BACKGROUND Subchorionic hematoma(SCH)is a common complication in early pregnancy characterized by the accumulation of blood between the uterine wall and the chorionic membrane.SCH can lead to adverse pregnancy outcome...BACKGROUND Subchorionic hematoma(SCH)is a common complication in early pregnancy characterized by the accumulation of blood between the uterine wall and the chorionic membrane.SCH can lead to adverse pregnancy outcomes such as miscarriage,preterm birth,and other complications.Early detection and accurate assessment of SCH are crucial for appropriate management and improved pregnancy outcomes.AIM To evaluate the diagnostic efficacy of virtual organ computer-assisted analysis(VOCAL)in measuring the volume ratio of SCH to gestational sac(GS)combined with serum progesterone on early pregnancy outcomes in patients with SCH.METHODS A total of 153 patients with SCH in their first-trimester pregnancies between 6 and 11 wk were enrolled.All patients were followed up until a gestational age of 20 wk.The parameters of transvaginal two-dimensional ultrasound,including the circumference of SCH(Cs),surface area of SCH(Ss),circumference of GS(Cg),and surface area of GS(Sg),and the parameters of VOCAL with transvaginal three-dimensional ultrasound,including the three-dimensional volume of SCH(3DVs)and GS(3DVg),were recorded.The size of the SCH and its ratio to the GS size(Cs/Cg,Ss/Sg,3DVs/3DVg)were recorded and compared.RESULTS Compared with those in the normal pregnancy group,the adverse pregnancy group had higher Cs/Cg,Ss/Sg,and 3DVs/3DVg ratios(P<0.05).When 3DVs/3DVg was 0.220,the highest predictive performance predicted adverse pregnancy outcomes,resulting in an AUC of 0.767,and the sensitivity,specificity were 70.2%,75%respectively.VOCAL measuring 3DVs/3DVg combined with serum progesterone gave a diagnostic AUC of 0.824 for early pregnancy outcome in SCH patients,with a high sensitivity of 82.1%and a specificity of 72.1%,which showed a significant difference between AUC.CONCLUSION VOCAL-measured 3DVs/3DVg effectively quantifies the severity of SCH,while combined serum progesterone better predicts adverse pregnancy outcomes.展开更多
Objective: Comparison of vaginal progesterone (VP) versus VP and intermittent intramuscular progesterone (IMP) use in frozen/thawed blastocyst transfer cycles. Study Design: A single center retrospective analyses of 4...Objective: Comparison of vaginal progesterone (VP) versus VP and intermittent intramuscular progesterone (IMP) use in frozen/thawed blastocyst transfer cycles. Study Design: A single center retrospective analyses of 470 elective FET cycles which were performed between January 2015 and September 2019 were evaluated. Patients were divided into two groups. Control group was consisted of VP (n = 272), the study group was consisted of VP plus IMP (n = 198) users. Results: The number of transfer attempts in control and study groups was 272 and 198, respectively. Age (29.8 ± 4 vs 30.6 ± 4;p = 0.09), BMI (22 ± 2 vs 21.9 ± 3;p = 0.79) and the number of transferred embryos (1.4 ± 0.5 vs 1.4 ± 0.5;p = 0.48) were comparable between groups. Altough, implantation rates (43.7% vs 43.6%;p = 0.9), ectopic pregnancy (0.8% vs 0.3%;p = 0.46) and abortion rates (8.2% vs 4.8%;p = 0.07) were similar. Biochemical pregnancy rate (8.4% vs 3.4% p = 0.01) in control group and ongoing pregnancy rate (OPR) (27.9% vs 38.1%;p = 0.005) in study group were significantly higher. Conclusion: Within the FET cycles in which good quality blastocyst are being transferred additional IMP supplementation to VP may increase OPR while reducing the biochemical pregnancy rate.展开更多
Background and Aims: Urinary tract infections (UTIs) are common among pregnant women and major predisposing factors for pyelonephritis linked to obstetrical complications including preterm labour and low infants’ bir...Background and Aims: Urinary tract infections (UTIs) are common among pregnant women and major predisposing factors for pyelonephritis linked to obstetrical complications including preterm labour and low infants’ birth weights. This study sought to determine the relationship(s) between pregnancy trimesters, UTIs and changes in progesterone levels among pregnant women. Materials and Methods: The study was conducted in 2016 at Moi Teaching and Referral Hospital (MTRH) antenatal clinic which is a referral facility that attends to patients from most Counties in western region of Kenya. A cross-sectional study design was used to collect blood and urine specimens from 78 participants. Blood was used to determine progesterone levels using ELISA technique and urine cultures with bacterial colony counts ≥ 10<sup>5</sup> were appropriately identified to species level. Trimester periods and participants’ demographic information were obtained using a structured questionnaire. Results: Culture results showed that the most abundant bacterial species isolated in urine from the pregnant women was Escherechia coli (63.7%). The more affected age-group was women between 30 - 39 years during trimester three, suggesting that bacterial colonization of genital track occurred more frequently in older compared to the younger women. There was an exponential increase in progesterone levels among the pregnant women during trimester three compared to other trimesters, although these increases occurred independent of age. However, high levels of progesterone among pregnant women in third trimester corresponded with increased number of E. coli causing UTI. Conclusion: The results showed that progesterone levels increase with trimester and the most prevalent bacteria associated with this was E. coli even though age and increase in progesterone levels had no significant impact on E. coli infection.展开更多
Progesterone(1) was biotransformed into the title compound 12β,15α-dihydroxy-progesterone(2) with Colletotrichum lini AS3.4486.The biotransformation process was monitored with HPLC.The structure of 2 was determi...Progesterone(1) was biotransformed into the title compound 12β,15α-dihydroxy-progesterone(2) with Colletotrichum lini AS3.4486.The biotransformation process was monitored with HPLC.The structure of 2 was determined by 1H NMR,13C NMR,ESI-MS and single-crystal X-ray diffraction.The crystal of the compound belongs to orthorhombic,space group P212121 with a = 8.0671(9),b = 12.3970(15),c = 18.532(3) ,Z = 4,V = 1853.3(4)3,Dc = 1.242 mg/m3,μ = 0.084 mm-1,F(000) = 752,R = 0.0373 and wR = 0.0850.Single-crystal X-ray diffraction analysis reveals that a 1D supramolecular structure of 2 has been constructed by multiply intermolecular O(2)-H(2)…O(4) and O(3)-H(3)…O(2) H-bonding interactions.展开更多
We previously investigated the progesterone metabolite 5β-dihydroprogesterone (5βDHP) in relation to human parturition at term, demonstrating that peripheral venous concentrations decrease in association with the on...We previously investigated the progesterone metabolite 5β-dihydroprogesterone (5βDHP) in relation to human parturition at term, demonstrating that peripheral venous concentrations decrease in association with the onset of spontaneous labour. In this study our aim was to determine if 5βDHP concentrations were lower in women presenting in spontaneous preterm labour than in controls matched for gestational age. Blood samples were obtained from women presenting in spontaneous preterm labour (n = 20). The diagnosis was made on the presence of regular contractions and cervical effacement and dilatation of at least 3 cms. All women in the preterm labour group delivered before 37 weeks gestation. Blood samples were then obtained from controls, closely matched for gestational age with uncomplicated pregnancies. The preterm labour group was further stratified by cause into three groups, chorioamnionitis (n = 5), abruption (n = 4) and idiopathic (n = 11). Following organic solvent extraction, steroids were separated by HPLC and 5βDHP quantified by radioimmunoassay. Women in the idiopathic preterm labour group were found to have significantly lower circulating concentrations of 5βDHP than controls展开更多
Objective:To systematically evaluate the efficacy and safety of didroxyprogesterone combined with progesterone in the treatment of luteal insufficiency abortion.Methods:We searched CNKI database,VIP database,Wanfang d...Objective:To systematically evaluate the efficacy and safety of didroxyprogesterone combined with progesterone in the treatment of luteal insufficiency abortion.Methods:We searched CNKI database,VIP database,Wanfang database,PubMed database,EMBASE database and Cochrane library database for literatures on the treatment of luteal insufficiency-induced abortion with didroxyprogesterone and progesterone.Meta-analysis was performed using Revman 5.3 software after literature extraction and further quality evaluation.Results:Ten randomized controlled trial-related articles that describe studies on a total of 1145 patients,570 in the combination group and 575 in the control group,were included.The results of meta-analysis showed that combination therapy could improve the effective rate of fetal protection(OR=0.14,95%CI[0.07,0.27],P<0.00001).The safety of the combination group was significantly higher than that of the control group(OR=3.09,95%CI[1.13,8.48],P=0.03).Conclusion:To sum up,compared with the control group,the combination of progesterone and progesterone is more effective and safer in the treatment of luteal insufficiency abortion.However,the sample size of the data is relatively small and the quality of the literature is low.This conclusion still needs to be further verified in high-quality randomized controlled trials that involve large samples.展开更多
Objective:To observe preventive and therapeutic effects and the mechanism of actions on Zishen Yutai pill combined with progesterone on threatened abortion in rats.Methods:After pregnancy,50 SPF female SD rats were se...Objective:To observe preventive and therapeutic effects and the mechanism of actions on Zishen Yutai pill combined with progesterone on threatened abortion in rats.Methods:After pregnancy,50 SPF female SD rats were selected and divided into control group,model group,progesterone group,Zishen Yutai pill group,and progesterone plus Zishen Yutai pill group(combination group),with 10 rats in each group.The rats of control group and abortion model group were lavaged with 2 mL/kg normal saline on pregnancy day 1 for continuous 10 days.Rats in Zishen Yutai pill group were given 1.575 g/kg/d of Zishen Yutai pill for intragastric administration for continuous 10 days.Rats in progesterone group were given intramuscular injection treatment of 0.1 mL/d progestin,continuous for 10 days.Rats in combination group were given injection therapy of aqueous solution of Zishen Yutai pill for continuous 10 days,and other treatments were the same as previous two groups.Abortion model were established then and live births,numbers of abortion and average rate of abortion were compared between the five groups.Peripheral blood was collected to detect the estradiol(E2) and progestational hormone(P),and obtain ratio of Th1/Th2 cytokines(IL-2,INF-γ,IL-4,IL-10).Results:Significant more live births of rats were found in the control group compared with other four groups(P<0.05).The numbers of live births of the rats in abortion model group were significantly less than that of progesterone group,Zishen Yutai pill group and joint group(P<0.05).The numbers of live births of rats in joint group were significant more than that of progesterone group and Zishen Yutai pill group.The serum E2 level of P of rats in the control group,progesterone group,Zishen Yutai pill group and joint group were significant higher than that of abortion model group(P<0.05).Serum levels of E2 and P of rats in the control group,progesterone group,Zishen Yutai pill group and joint group were not significant different(P>0.05) but these levels in the control group and Zishen Yutai pill group were significant lower than that of progesterone group and joint group(P<0.05).The maternal-fetal interface IL-4/IL-2,IL-10 / IL-2 of model group were balanced deviating to Th1,while the IL-4/IL-2,IL-10/IL-2 of progesterone group,Zishen Yutai pill group and joint group were balanced deviating to Th2,and joint group' deviation was better than progesterone group and Zishen Yutai pill group(P<0.05).Conclusions:Zishen Yutai pill combined with progesterone has a significant control effect for threatened abortion,which can obviously increase contents of maternal serums E2 and P,and regulate the Thl/Th2 balance with a remarkable effect.展开更多
Objective Traumatic brain injury (TBI) is one of the leading causes of morbidity and mortality in young people. Inflammatory cytokines play an important part in the pathophysiology of TBI. Recent studies demonstrate...Objective Traumatic brain injury (TBI) is one of the leading causes of morbidity and mortality in young people. Inflammatory cytokines play an important part in the pathophysiology of TBI. Recent studies demonstrate that progesterone significantly reduces cerebral edema and enhances functional recovery from TBI and stroke in several animal models. This study was designed to investigate the inhibitory effect of progesterone on inflammatory response after traumatic brain injury. Methods Progesterone was injected intraperitoneally using rats as a model of traumatic brain injury, and Western blot technique was applied to detect the expression of three inflammation-related factors: nuclear factor kappa B p65 (NFκB p65), glial fibrillary acidic protein (GFAP), and tumor necrosis factor-α (TNF-α). The water content of injured brain was also examined. A neurological severity score was recorded to evaluate the effect of progesterone on neurodeficit recovery. Results NFκB p65, GFAP, and TNF-α were increased in all injured animals. In rats treated with progesterone, the expression level of NFκB p65 and TNF-α were reduced significantly in comparison with vehicle-treated rats. However, progesterone did not alter the expression of GFAP in the injured rats. Progesterone also reduced the water content of injured brain and the lesion volume. In addition, progesterone-treated injured rats showed significant improvements in the Neurological Severity Score test, compared with vehicle-treated ones. Conclusions Progesterone inhibits the inflammatory response after experimental traumatic brain injury and mitigates the severity of brain damage.展开更多
In this study, human umbilical cord mesenchymal stem cells from full-term neonates born by vagina delivery were cultured in medium containing 150 mg/mL of brain tissue extracts from Sprague-Dawley rats (to mimic the ...In this study, human umbilical cord mesenchymal stem cells from full-term neonates born by vagina delivery were cultured in medium containing 150 mg/mL of brain tissue extracts from Sprague-Dawley rats (to mimic the brain microenvironment). Immunocytochemical analysis demonstrated that the cells differentiated into neuron-like cells. To evaluate the effects of progesterone as a neurosteroid on the neuronal differentiation of human umbilical cord mesenchymal stem cells, we cultured the cells in medium containing progesterone (0.1, 1, 10 pM) in addition to brain tissue extracts. Reverse transcription-PCR and flow cytometric analysis of neuron specific enolase-positive cells revealed that the percentages of these cells increased significantly following progesterone treatment, with the optimal progesterone concentration for neuron-like differentiation being 1 tJM. These results suggest that progesterone can enhance the neuronal differentiation of human umbilical cord mesenchymal stem cells in culture medium containing brain tissue extracts to mimic the brain microenvironment.展开更多
AIM To investigate the clinicopathological significance of progesterone receptor membrane component 1(PGRMC1) and PGRMC2 in hepatocellular carcinoma(HCC). METHODS We performed immunohistochemical staining to evaluate ...AIM To investigate the clinicopathological significance of progesterone receptor membrane component 1(PGRMC1) and PGRMC2 in hepatocellular carcinoma(HCC). METHODS We performed immunohistochemical staining to evaluate the estrogen receptor(ER), progesterone receptor(PR), PGRMC1, and PGRMC2 in a clinical cohort consisting of 89 paired HCC and non-tumor liver samples. We also analyzed HCC data(n = 373) from The Cancer Genome Atlas(TCGA). We correlated the expression status of PGRMC1 and PGRMC2 with clinicopathological indicators and the clinical outcomes of the HCC patients. We knocked down or overexpressed PGRMC1 in HCC cell lines to evaluate its biological significance in HCC cell proliferation, differentiation, migration, and invasion. RESULTS We found that few HCC cases expressed ER(5.6%) and PR(4.5%). In contrast, most HCC cases expressed PGRMC1(89.9%) and PGRMC2(100%). PGRMC1 and PGRMC2 exhibited significantly lower expression in tumor tissue than in non-tumor tissue(P < 0.001). Lower PGRMC1 expression in HCC was significantly associated with higher serum alpha-fetoprotein expression(P = 0.004), poorer tumor differentiation(P = 0.045) and liver capsule penetration(P = 0.038). Low PGRMC1 expression was an independent predictor for worse disease-free survival(P = 0.002, HR = 2.384,CI: 1.377-4.128) in our cases, as well as in the TCGA cohort(P < 0.001, HR = 2.857, CI: 1.781-4.584). The expression of PGRMC2 did not relate to patient outcome. PGRMC1 knockdown promoted a poorly differentiated phenotype and proliferation of HCC cells in vitro, while PGRMC1 overexpression caused the opposite effects.CONCLUSION PGRMC1 is a non-classical hormonal receptor that negatively regulates hepatocarcinogenesis. PGRMC1 down-regulation is associated with progression of HCC and is a poor prognostic indicator.展开更多
Distribution and accumulation of Nd, and its effect on secretion of progesterone in mice were studied using radioisotope tracer ((()^(147)Nd)) technique. Following single intraperitoneal administration of neodymium tr...Distribution and accumulation of Nd, and its effect on secretion of progesterone in mice were studied using radioisotope tracer ((()^(147)Nd)) technique. Following single intraperitoneal administration of neodymium traced with (()^(147)Nd) at a dose of 200 mg·kg^(-1), uneven distribution of the radioactive Nd occurred in various tissues and organs. Much amount of (()^(147)Nd) accumulates in the bone, and the residue increases with the lapse of time. Some amount of radioactivity was also detected in eyes, blood and brain, but the accumulation decreased with the time due to excretion and re-distribution in mice. In comparison with controls, concentration of progesterone is found to be significantly lower in the serum of administered mice, indicating a significantly inhibitory effect of Nd on secretion of progesterone.展开更多
Progesterone has nongenomic effects on inducible nitric oxide synthase(iNOS),which is mediated by mitogen activated protein kinase(MAPK)pathways.This effect is supposed to have some potential association with asymptom...Progesterone has nongenomic effects on inducible nitric oxide synthase(iNOS),which is mediated by mitogen activated protein kinase(MAPK)pathways.This effect is supposed to have some potential association with asymptomatic gonococcal infections in women by immunological depression.In this study,polymorphonuclear leukocytes(PMNs)challenged by gonococci were used to study the nongenomic effects of progesterone.The activation of iNOS was assessed by measuring [3H] L-arginine converses to [3H] L-citrulline,and t...展开更多
To evaluate the effect of GnRHa induced superovulation protocol on endometrial morphology and function. Material & Methods Forty ICR mice were randomly allocated into 4 groups, among them, 2 experimental gro...To evaluate the effect of GnRHa induced superovulation protocol on endometrial morphology and function. Material & Methods Forty ICR mice were randomly allocated into 4 groups, among them, 2 experimental groups were injected with GnRHa+HMG+hCG, another 2 groups were given saline of same volume as control group. The uterine tissues were investigated at 24 h and 48 h after administration (experimental group) or ovulation (control group).The endometrial thickness, the size of gland and glandular lumen, the total area of glandular cells, the average height of glandular epithelium were measured from routine histological slides using computerized image analysis. The SP immunohistochemistry techniques with monoclonal antibodies were employed to semi quantitatively analize the estrogen receptor (ER) and progesterone receptor (PR) in glandular cells. Results The endometrial thickness was not significantly different between experimental groups and control groups at 24 h and 48 h (P>0.05).The average area, perimeter, maximal diameter of single gland and glandular lumen, the total area, average height of glandular epithelium in experimental groups were significantly smaller than those of in control groups at equivalent time stages (all P<0.01). The asynchronous development of gland epithelium and stroma cells, namely, pesudostratified glandular epithelium and predecidual changes of stroma cells were seen at same time in experimental groups. The positive percentage (%) and expression intense of ER and PR in glandular epithelium cells were significantly lower in experimental groups than in control groups (P<0.05). Conclusion The protocol with GnRHa had a negative effect on endometrial histological structure and down regulated the express of ER and PR, suggesting that this protocol effect on the endometrial morphology and function and could not facilitate the formation of a physiologic endometrium completely, which may be one of the causes of low pregnancy rates.展开更多
A new role has emerged for progesterone after discovering its potent actions away from reproduction in both the central and the peripheral nervous system. The aim of the present report is to discuss progesterone’s me...A new role has emerged for progesterone after discovering its potent actions away from reproduction in both the central and the peripheral nervous system. The aim of the present report is to discuss progesterone’s mechanisms of action involved in myelination, remyelination and neuroinflammation. The pivotal role of the classic progesterone receptor is described and evidence is compiled about progesterone’s direct effects on oligodendrocyte linage and its indirect effects on oligodendrocyte precursor cell differentiation by decreasing the neuroinflammatory environment.展开更多
Can progesterone be a better alternative to dexamethasone for use in routine brain surgery? Surgical brain injury (SBI) is a form of brain trauma caused by various forms of neurosurgical interventions including bra...Can progesterone be a better alternative to dexamethasone for use in routine brain surgery? Surgical brain injury (SBI) is a form of brain trauma caused by various forms of neurosurgical interventions including brain tumor excision, evacuation of intracere- bral hemorrhage and brain lobectomv (e.g., in epililepsv surger).展开更多
Background:Administration of progesterone(P4)to ewes during the first 9 to 12 days of pregnancy accelerates blastocyst development by day 12 of pregnancy,likely due to P4-induced up-regulation of key genes in uterine ...Background:Administration of progesterone(P4)to ewes during the first 9 to 12 days of pregnancy accelerates blastocyst development by day 12 of pregnancy,likely due to P4-induced up-regulation of key genes in uterine epithelia responsible for secretion and transport of components of histotroph into the uterine lumen.This study determined if acceleration of blastocyst development induced by exogenous P4 during the pre-implantation period affects fetal-placental development on day 125 of pregnancy.Suffolk ewes(n=35)were mated to fertile rams and assigned randomly to receive daily intramuscular injections of either corn oil vehicle(CO,n=18)or 25 mg progesterone in CO(P4,n=17)for the first 8 days of pregnancy.All ewes were hysterectomized on day 125 of pregnancy and:1)fetal and placental weights and measurements were recorded;2)endometrial and placental tissues were analyzed for the expression of candidate mRNAs involved in nutrient transport and arginine metabolism;and 3)maternal plasma,fetal plasma,allantoic fluid,and amniotic fluid were analyzed for amino acids,agmatine,polyamines,glucose,and fructose.Results:Treatment of ewes with exogenous P4 did not alter fetal or placental growth,but increased amounts of aspartate and arginine in allantoic fluid and amniotic fluid,respectively.Ewes that received exogenous P4 had greater expression of mRNAs for SLC7A1,SLC7A2,SLC2A1,AGMAT,and ODC1 in endometria,as well as SLC1A4,SLC2A5,SLC2A8 and ODC1 in placentomes.In addition,AZIN2 protein was immunolocalized to uterine luminal and glandular epithelia in P4-treated ewes,whereas AZIN2 localized only to uterine luminal epithelia in CO-treated ewes.Conclusions:This study revealed that exogenous P4 administered in early pregnancy influenced expression of selected genes for nutrient transporters and the expression of a protein involved in polyamine synthesis on day 125 of pregnancy,suggesting a‘programming’effect of P4 on gene expression that affected the composition of nutrients in fetal-placental fluids.展开更多
Aim: To evaluate the benefits and hazards of routine progesterone supplementation in threatened abortion and whether it is a sound practice or not. Materials and Methods: This study was conducted at Obstetrics and Gyn...Aim: To evaluate the benefits and hazards of routine progesterone supplementation in threatened abortion and whether it is a sound practice or not. Materials and Methods: This study was conducted at Obstetrics and Gynecology Department, Tanta University in the period from January 2018 to December 2018. Eligible patients (n = 190) were randomly allocated into 2 groups: study group who will receive progesterone supplementation (prog. group) and control group who will receive no treatment (place. group). Results: No significant differences were found between both groups regarding all demographic data and pregnancy characteristics. Abortions were higher in place. group 17 (23.94%) than in prog. group 12 (16.44%) with no significant difference p value = 0.263. The incidence of preterm labour was also higher in the place. group 22 (30.99%) in comparison to the prog. group 17 (23.29%) with no significant difference p value = 0.300. Conclusion: Progesterone supplementation in threatened abortion was not beneficial although it reduced abortion and preterm labour rates.展开更多
There is currently no standard pharmacological treatment for spinal cord injury. Here, we suggest that progesterone, a steroid hormone, may be a promising therapeutical candidate as it is already for traumatic brain i...There is currently no standard pharmacological treatment for spinal cord injury. Here, we suggest that progesterone, a steroid hormone, may be a promising therapeutical candidate as it is already for traumatic brain injury, where it has reached phase II clinical trials. We rely on previous works showing anti-inflammatory, neuroprotective and promyelinating roles for progesterone after spinal cord injury and in our recent paper, in which we demonstrate that progesterone diminishes lesion, preserves white matter integrity and improves locomotor recovery in a clinically relevant model of spinal cord lesion.展开更多
There are currently no federally approved neuroprotective agents to treat traumatic brain injury. Progesterone, a hydrophobic steroid hormone, has been shown in recent studies to exhibit neu-roprotective effects in co...There are currently no federally approved neuroprotective agents to treat traumatic brain injury. Progesterone, a hydrophobic steroid hormone, has been shown in recent studies to exhibit neu-roprotective effects in controlled cortical impact rat models. Akt is a protein kinase known to play a role in cell signaling pathways that reduce edema, inlfammation, apoptosis, and promote cell growth in the brain. This study aims to determine if progesterone modulates the phosphor-ylation of Aktvia its threonine 308 phosphorylation site. Phosphorylation at the threonine 308 site is one of several sites responsible for activating Akt and enabling the protein kinase to carry out its neuroprotective effects. To assess the effects of progesterone on Akt phosphorylation, C57BL/6 mice were treated with progesterone (8 mg/kg) at 1 (intraperitonally), 6, 24, and 48 hours (subcutaneously) post closed-skull traumatic brain injury. The hippocampus was harvest-ed at 72 hours post injury and prepared for western blot analysis. Traumatic brain injury caused a signiifcant decrease in Akt phosphorylation compared to sham operation. However, mice treat-ed with progesterone following traumatic brain injury had an increase in phosphorylation of Akt compared to traumatic brain injury vehicle. Our ifndings suggest that progesterone is a viable treatment option for activating neuroprotective pathways after traumatic brain injury.展开更多
BACKGROUND: Coriaria lactone-activated astrocytes released bioactive substances that eventually caused epilepsy. OBJECTIVE: It has been suggested that activated astrocytes alter the expression of the estrogen recept...BACKGROUND: Coriaria lactone-activated astrocytes released bioactive substances that eventually caused epilepsy. OBJECTIVE: It has been suggested that activated astrocytes alter the expression of the estrogen receptor and progesterone receptor by releasing bioactive substances during epilepsy, thereby affecting neuronal activity in the brain. This study was designed to observe the expression of the estrogen receptor and the progesterone receptor in rat brain following lateral ventricle injection of coriaria lactone-activated, astrocyte-conditioned medium. DESIGN AND SETTING: This immunohistochemical, randomized, controlled, animal study was conducted at the Department of Pathology, Hospital Affiliated to Binzhou Medical College, China. MATERIAL: Coriaria lactone was provided by Huaxi Pharmaceutical Factory, China. METHODS: Forty adult, healthy, male, Sprague Dawley rats were randomly assigned into two groups. Astrocyte-conditioned medium (10 μ L) was injected into rat lateral ventricle in the control group (n = 8). Coriaria lactone-activated, astrocyte-conditioned medium (10 μL) was infused into the rat lateral ventricle in the coriaria lactone group (n = 32). At 2, 4, 8 and 12 hours following injection, rats were sacrificed and subjected to immunohistochemistry. Eight rats were studied at each time point. MAIN OUTCOME MEASURES: Behavioral changes were observed in rats of both groups. Expression of the estrogen receptor and the progesterone receptor in rat cortical and hippocampal neurons was measured using immunohistochemistry. RESULTS: Four hours after injection, estrogen receptor levels in rat cortical and hippocampal neurons were significantly higher in the coriaria lactone group than in the control group (P 〈 0.05). Progesterone receptor levels were significantly lower in the coriaria lactone group than in the control group (P 〈 0.05). Seizures were not observed in the control group. In the coriaria lactone group, convulsions appeared 30 minutes after injection; seizures reached grade Ⅲ at 45 minutes rat behavior was nearly normal at 2 hours. CONCLUSION: Activated astrocytes can induce seizures in the rat by enhancing estrogen receptor expression and decreasing progesterone receptor expression in cerebral cortical and hippocampal neurons.展开更多
文摘BACKGROUND Subchorionic hematoma(SCH)is a common complication in early pregnancy characterized by the accumulation of blood between the uterine wall and the chorionic membrane.SCH can lead to adverse pregnancy outcomes such as miscarriage,preterm birth,and other complications.Early detection and accurate assessment of SCH are crucial for appropriate management and improved pregnancy outcomes.AIM To evaluate the diagnostic efficacy of virtual organ computer-assisted analysis(VOCAL)in measuring the volume ratio of SCH to gestational sac(GS)combined with serum progesterone on early pregnancy outcomes in patients with SCH.METHODS A total of 153 patients with SCH in their first-trimester pregnancies between 6 and 11 wk were enrolled.All patients were followed up until a gestational age of 20 wk.The parameters of transvaginal two-dimensional ultrasound,including the circumference of SCH(Cs),surface area of SCH(Ss),circumference of GS(Cg),and surface area of GS(Sg),and the parameters of VOCAL with transvaginal three-dimensional ultrasound,including the three-dimensional volume of SCH(3DVs)and GS(3DVg),were recorded.The size of the SCH and its ratio to the GS size(Cs/Cg,Ss/Sg,3DVs/3DVg)were recorded and compared.RESULTS Compared with those in the normal pregnancy group,the adverse pregnancy group had higher Cs/Cg,Ss/Sg,and 3DVs/3DVg ratios(P<0.05).When 3DVs/3DVg was 0.220,the highest predictive performance predicted adverse pregnancy outcomes,resulting in an AUC of 0.767,and the sensitivity,specificity were 70.2%,75%respectively.VOCAL measuring 3DVs/3DVg combined with serum progesterone gave a diagnostic AUC of 0.824 for early pregnancy outcome in SCH patients,with a high sensitivity of 82.1%and a specificity of 72.1%,which showed a significant difference between AUC.CONCLUSION VOCAL-measured 3DVs/3DVg effectively quantifies the severity of SCH,while combined serum progesterone better predicts adverse pregnancy outcomes.
文摘Objective: Comparison of vaginal progesterone (VP) versus VP and intermittent intramuscular progesterone (IMP) use in frozen/thawed blastocyst transfer cycles. Study Design: A single center retrospective analyses of 470 elective FET cycles which were performed between January 2015 and September 2019 were evaluated. Patients were divided into two groups. Control group was consisted of VP (n = 272), the study group was consisted of VP plus IMP (n = 198) users. Results: The number of transfer attempts in control and study groups was 272 and 198, respectively. Age (29.8 ± 4 vs 30.6 ± 4;p = 0.09), BMI (22 ± 2 vs 21.9 ± 3;p = 0.79) and the number of transferred embryos (1.4 ± 0.5 vs 1.4 ± 0.5;p = 0.48) were comparable between groups. Altough, implantation rates (43.7% vs 43.6%;p = 0.9), ectopic pregnancy (0.8% vs 0.3%;p = 0.46) and abortion rates (8.2% vs 4.8%;p = 0.07) were similar. Biochemical pregnancy rate (8.4% vs 3.4% p = 0.01) in control group and ongoing pregnancy rate (OPR) (27.9% vs 38.1%;p = 0.005) in study group were significantly higher. Conclusion: Within the FET cycles in which good quality blastocyst are being transferred additional IMP supplementation to VP may increase OPR while reducing the biochemical pregnancy rate.
文摘Background and Aims: Urinary tract infections (UTIs) are common among pregnant women and major predisposing factors for pyelonephritis linked to obstetrical complications including preterm labour and low infants’ birth weights. This study sought to determine the relationship(s) between pregnancy trimesters, UTIs and changes in progesterone levels among pregnant women. Materials and Methods: The study was conducted in 2016 at Moi Teaching and Referral Hospital (MTRH) antenatal clinic which is a referral facility that attends to patients from most Counties in western region of Kenya. A cross-sectional study design was used to collect blood and urine specimens from 78 participants. Blood was used to determine progesterone levels using ELISA technique and urine cultures with bacterial colony counts ≥ 10<sup>5</sup> were appropriately identified to species level. Trimester periods and participants’ demographic information were obtained using a structured questionnaire. Results: Culture results showed that the most abundant bacterial species isolated in urine from the pregnant women was Escherechia coli (63.7%). The more affected age-group was women between 30 - 39 years during trimester three, suggesting that bacterial colonization of genital track occurred more frequently in older compared to the younger women. There was an exponential increase in progesterone levels among the pregnant women during trimester three compared to other trimesters, although these increases occurred independent of age. However, high levels of progesterone among pregnant women in third trimester corresponded with increased number of E. coli causing UTI. Conclusion: The results showed that progesterone levels increase with trimester and the most prevalent bacteria associated with this was E. coli even though age and increase in progesterone levels had no significant impact on E. coli infection.
基金supported by the Natural Science Foundation of Tianjin (Nos. 08JCZDJC15200 and 11JGYBJC14300)the Program for New Century Excellent Talents in University (No. NCET-08-0911)
文摘Progesterone(1) was biotransformed into the title compound 12β,15α-dihydroxy-progesterone(2) with Colletotrichum lini AS3.4486.The biotransformation process was monitored with HPLC.The structure of 2 was determined by 1H NMR,13C NMR,ESI-MS and single-crystal X-ray diffraction.The crystal of the compound belongs to orthorhombic,space group P212121 with a = 8.0671(9),b = 12.3970(15),c = 18.532(3) ,Z = 4,V = 1853.3(4)3,Dc = 1.242 mg/m3,μ = 0.084 mm-1,F(000) = 752,R = 0.0373 and wR = 0.0850.Single-crystal X-ray diffraction analysis reveals that a 1D supramolecular structure of 2 has been constructed by multiply intermolecular O(2)-H(2)…O(4) and O(3)-H(3)…O(2) H-bonding interactions.
文摘We previously investigated the progesterone metabolite 5β-dihydroprogesterone (5βDHP) in relation to human parturition at term, demonstrating that peripheral venous concentrations decrease in association with the onset of spontaneous labour. In this study our aim was to determine if 5βDHP concentrations were lower in women presenting in spontaneous preterm labour than in controls matched for gestational age. Blood samples were obtained from women presenting in spontaneous preterm labour (n = 20). The diagnosis was made on the presence of regular contractions and cervical effacement and dilatation of at least 3 cms. All women in the preterm labour group delivered before 37 weeks gestation. Blood samples were then obtained from controls, closely matched for gestational age with uncomplicated pregnancies. The preterm labour group was further stratified by cause into three groups, chorioamnionitis (n = 5), abruption (n = 4) and idiopathic (n = 11). Following organic solvent extraction, steroids were separated by HPLC and 5βDHP quantified by radioimmunoassay. Women in the idiopathic preterm labour group were found to have significantly lower circulating concentrations of 5βDHP than controls
基金Social Development Science and Technology Project(Project name:Clinical study on the effect of electroacupuncture combined with walking through the meridian on body mass index,glucose metabolism and reproductive endocrine in patients with obese polycystic ovary syndromeProject no.:2016SF-362)Special Project of Natural Science(Project name:Association of endometrial precancerous lesions with insulin resistance and adiponectin based on high incidence of diabetes mellitus,Project no.:13JK0800)。
文摘Objective:To systematically evaluate the efficacy and safety of didroxyprogesterone combined with progesterone in the treatment of luteal insufficiency abortion.Methods:We searched CNKI database,VIP database,Wanfang database,PubMed database,EMBASE database and Cochrane library database for literatures on the treatment of luteal insufficiency-induced abortion with didroxyprogesterone and progesterone.Meta-analysis was performed using Revman 5.3 software after literature extraction and further quality evaluation.Results:Ten randomized controlled trial-related articles that describe studies on a total of 1145 patients,570 in the combination group and 575 in the control group,were included.The results of meta-analysis showed that combination therapy could improve the effective rate of fetal protection(OR=0.14,95%CI[0.07,0.27],P<0.00001).The safety of the combination group was significantly higher than that of the control group(OR=3.09,95%CI[1.13,8.48],P=0.03).Conclusion:To sum up,compared with the control group,the combination of progesterone and progesterone is more effective and safer in the treatment of luteal insufficiency abortion.However,the sample size of the data is relatively small and the quality of the literature is low.This conclusion still needs to be further verified in high-quality randomized controlled trials that involve large samples.
基金supported by Natural Sciences Fund of Zhejiang Province(grant number:LY14H040011)Subject of Zhejiang Provincial Administration of traditional Chinese Medicine(grant number:2013ZB058)
文摘Objective:To observe preventive and therapeutic effects and the mechanism of actions on Zishen Yutai pill combined with progesterone on threatened abortion in rats.Methods:After pregnancy,50 SPF female SD rats were selected and divided into control group,model group,progesterone group,Zishen Yutai pill group,and progesterone plus Zishen Yutai pill group(combination group),with 10 rats in each group.The rats of control group and abortion model group were lavaged with 2 mL/kg normal saline on pregnancy day 1 for continuous 10 days.Rats in Zishen Yutai pill group were given 1.575 g/kg/d of Zishen Yutai pill for intragastric administration for continuous 10 days.Rats in progesterone group were given intramuscular injection treatment of 0.1 mL/d progestin,continuous for 10 days.Rats in combination group were given injection therapy of aqueous solution of Zishen Yutai pill for continuous 10 days,and other treatments were the same as previous two groups.Abortion model were established then and live births,numbers of abortion and average rate of abortion were compared between the five groups.Peripheral blood was collected to detect the estradiol(E2) and progestational hormone(P),and obtain ratio of Th1/Th2 cytokines(IL-2,INF-γ,IL-4,IL-10).Results:Significant more live births of rats were found in the control group compared with other four groups(P<0.05).The numbers of live births of the rats in abortion model group were significantly less than that of progesterone group,Zishen Yutai pill group and joint group(P<0.05).The numbers of live births of rats in joint group were significant more than that of progesterone group and Zishen Yutai pill group.The serum E2 level of P of rats in the control group,progesterone group,Zishen Yutai pill group and joint group were significant higher than that of abortion model group(P<0.05).Serum levels of E2 and P of rats in the control group,progesterone group,Zishen Yutai pill group and joint group were not significant different(P>0.05) but these levels in the control group and Zishen Yutai pill group were significant lower than that of progesterone group and joint group(P<0.05).The maternal-fetal interface IL-4/IL-2,IL-10 / IL-2 of model group were balanced deviating to Th1,while the IL-4/IL-2,IL-10/IL-2 of progesterone group,Zishen Yutai pill group and joint group were balanced deviating to Th2,and joint group' deviation was better than progesterone group and Zishen Yutai pill group(P<0.05).Conclusions:Zishen Yutai pill combined with progesterone has a significant control effect for threatened abortion,which can obviously increase contents of maternal serums E2 and P,and regulate the Thl/Th2 balance with a remarkable effect.
文摘Objective Traumatic brain injury (TBI) is one of the leading causes of morbidity and mortality in young people. Inflammatory cytokines play an important part in the pathophysiology of TBI. Recent studies demonstrate that progesterone significantly reduces cerebral edema and enhances functional recovery from TBI and stroke in several animal models. This study was designed to investigate the inhibitory effect of progesterone on inflammatory response after traumatic brain injury. Methods Progesterone was injected intraperitoneally using rats as a model of traumatic brain injury, and Western blot technique was applied to detect the expression of three inflammation-related factors: nuclear factor kappa B p65 (NFκB p65), glial fibrillary acidic protein (GFAP), and tumor necrosis factor-α (TNF-α). The water content of injured brain was also examined. A neurological severity score was recorded to evaluate the effect of progesterone on neurodeficit recovery. Results NFκB p65, GFAP, and TNF-α were increased in all injured animals. In rats treated with progesterone, the expression level of NFκB p65 and TNF-α were reduced significantly in comparison with vehicle-treated rats. However, progesterone did not alter the expression of GFAP in the injured rats. Progesterone also reduced the water content of injured brain and the lesion volume. In addition, progesterone-treated injured rats showed significant improvements in the Neurological Severity Score test, compared with vehicle-treated ones. Conclusions Progesterone inhibits the inflammatory response after experimental traumatic brain injury and mitigates the severity of brain damage.
基金supported by the Military Medical Research Program during the 12th Five-Year Plan Period, No.BWS11J002
文摘In this study, human umbilical cord mesenchymal stem cells from full-term neonates born by vagina delivery were cultured in medium containing 150 mg/mL of brain tissue extracts from Sprague-Dawley rats (to mimic the brain microenvironment). Immunocytochemical analysis demonstrated that the cells differentiated into neuron-like cells. To evaluate the effects of progesterone as a neurosteroid on the neuronal differentiation of human umbilical cord mesenchymal stem cells, we cultured the cells in medium containing progesterone (0.1, 1, 10 pM) in addition to brain tissue extracts. Reverse transcription-PCR and flow cytometric analysis of neuron specific enolase-positive cells revealed that the percentages of these cells increased significantly following progesterone treatment, with the optimal progesterone concentration for neuron-like differentiation being 1 tJM. These results suggest that progesterone can enhance the neuronal differentiation of human umbilical cord mesenchymal stem cells in culture medium containing brain tissue extracts to mimic the brain microenvironment.
基金Supported by the Ministry of Science and Technology,No.NSC102-2320-B-006-011.,No.MOST103-2320-B-006-021-MY2,and No.MOST105-2320-B-006-033 to Tsai HWNational Cheng Kung University Hospital,Taiwan,No.NCKUH-10406002 and No.NCKUH-10509001 to Tsai HW
文摘AIM To investigate the clinicopathological significance of progesterone receptor membrane component 1(PGRMC1) and PGRMC2 in hepatocellular carcinoma(HCC). METHODS We performed immunohistochemical staining to evaluate the estrogen receptor(ER), progesterone receptor(PR), PGRMC1, and PGRMC2 in a clinical cohort consisting of 89 paired HCC and non-tumor liver samples. We also analyzed HCC data(n = 373) from The Cancer Genome Atlas(TCGA). We correlated the expression status of PGRMC1 and PGRMC2 with clinicopathological indicators and the clinical outcomes of the HCC patients. We knocked down or overexpressed PGRMC1 in HCC cell lines to evaluate its biological significance in HCC cell proliferation, differentiation, migration, and invasion. RESULTS We found that few HCC cases expressed ER(5.6%) and PR(4.5%). In contrast, most HCC cases expressed PGRMC1(89.9%) and PGRMC2(100%). PGRMC1 and PGRMC2 exhibited significantly lower expression in tumor tissue than in non-tumor tissue(P < 0.001). Lower PGRMC1 expression in HCC was significantly associated with higher serum alpha-fetoprotein expression(P = 0.004), poorer tumor differentiation(P = 0.045) and liver capsule penetration(P = 0.038). Low PGRMC1 expression was an independent predictor for worse disease-free survival(P = 0.002, HR = 2.384,CI: 1.377-4.128) in our cases, as well as in the TCGA cohort(P < 0.001, HR = 2.857, CI: 1.781-4.584). The expression of PGRMC2 did not relate to patient outcome. PGRMC1 knockdown promoted a poorly differentiated phenotype and proliferation of HCC cells in vitro, while PGRMC1 overexpression caused the opposite effects.CONCLUSION PGRMC1 is a non-classical hormonal receptor that negatively regulates hepatocarcinogenesis. PGRMC1 down-regulation is associated with progression of HCC and is a poor prognostic indicator.
文摘Distribution and accumulation of Nd, and its effect on secretion of progesterone in mice were studied using radioisotope tracer ((()^(147)Nd)) technique. Following single intraperitoneal administration of neodymium traced with (()^(147)Nd) at a dose of 200 mg·kg^(-1), uneven distribution of the radioactive Nd occurred in various tissues and organs. Much amount of (()^(147)Nd) accumulates in the bone, and the residue increases with the lapse of time. Some amount of radioactivity was also detected in eyes, blood and brain, but the accumulation decreased with the time due to excretion and re-distribution in mice. In comparison with controls, concentration of progesterone is found to be significantly lower in the serum of administered mice, indicating a significantly inhibitory effect of Nd on secretion of progesterone.
基金supported by the Young Scientists Fund Program of National Natural Science Fund Program from National Natural Sciences Foundation of China(No.30371293)Medical Research Foundation of Guangdong Province of China(No.B2009193)
文摘Progesterone has nongenomic effects on inducible nitric oxide synthase(iNOS),which is mediated by mitogen activated protein kinase(MAPK)pathways.This effect is supposed to have some potential association with asymptomatic gonococcal infections in women by immunological depression.In this study,polymorphonuclear leukocytes(PMNs)challenged by gonococci were used to study the nongenomic effects of progesterone.The activation of iNOS was assessed by measuring [3H] L-arginine converses to [3H] L-citrulline,and t...
文摘To evaluate the effect of GnRHa induced superovulation protocol on endometrial morphology and function. Material & Methods Forty ICR mice were randomly allocated into 4 groups, among them, 2 experimental groups were injected with GnRHa+HMG+hCG, another 2 groups were given saline of same volume as control group. The uterine tissues were investigated at 24 h and 48 h after administration (experimental group) or ovulation (control group).The endometrial thickness, the size of gland and glandular lumen, the total area of glandular cells, the average height of glandular epithelium were measured from routine histological slides using computerized image analysis. The SP immunohistochemistry techniques with monoclonal antibodies were employed to semi quantitatively analize the estrogen receptor (ER) and progesterone receptor (PR) in glandular cells. Results The endometrial thickness was not significantly different between experimental groups and control groups at 24 h and 48 h (P>0.05).The average area, perimeter, maximal diameter of single gland and glandular lumen, the total area, average height of glandular epithelium in experimental groups were significantly smaller than those of in control groups at equivalent time stages (all P<0.01). The asynchronous development of gland epithelium and stroma cells, namely, pesudostratified glandular epithelium and predecidual changes of stroma cells were seen at same time in experimental groups. The positive percentage (%) and expression intense of ER and PR in glandular epithelium cells were significantly lower in experimental groups than in control groups (P<0.05). Conclusion The protocol with GnRHa had a negative effect on endometrial histological structure and down regulated the express of ER and PR, suggesting that this protocol effect on the endometrial morphology and function and could not facilitate the formation of a physiologic endometrium completely, which may be one of the causes of low pregnancy rates.
文摘A new role has emerged for progesterone after discovering its potent actions away from reproduction in both the central and the peripheral nervous system. The aim of the present report is to discuss progesterone’s mechanisms of action involved in myelination, remyelination and neuroinflammation. The pivotal role of the classic progesterone receptor is described and evidence is compiled about progesterone’s direct effects on oligodendrocyte linage and its indirect effects on oligodendrocyte precursor cell differentiation by decreasing the neuroinflammatory environment.
文摘Can progesterone be a better alternative to dexamethasone for use in routine brain surgery? Surgical brain injury (SBI) is a form of brain trauma caused by various forms of neurosurgical interventions including brain tumor excision, evacuation of intracere- bral hemorrhage and brain lobectomv (e.g., in epililepsv surger).
基金This research was supported by Agriculture and Food Research Initiative Competitive Grant no.2016-67015-24958 from the USDA National Institute of Food and AgricultureThis research was supported by Agriculture and Food Research Initiative Competitive Grant no.2016-67015-24958 from the USDA National Institute of Food and Agriculture.
文摘Background:Administration of progesterone(P4)to ewes during the first 9 to 12 days of pregnancy accelerates blastocyst development by day 12 of pregnancy,likely due to P4-induced up-regulation of key genes in uterine epithelia responsible for secretion and transport of components of histotroph into the uterine lumen.This study determined if acceleration of blastocyst development induced by exogenous P4 during the pre-implantation period affects fetal-placental development on day 125 of pregnancy.Suffolk ewes(n=35)were mated to fertile rams and assigned randomly to receive daily intramuscular injections of either corn oil vehicle(CO,n=18)or 25 mg progesterone in CO(P4,n=17)for the first 8 days of pregnancy.All ewes were hysterectomized on day 125 of pregnancy and:1)fetal and placental weights and measurements were recorded;2)endometrial and placental tissues were analyzed for the expression of candidate mRNAs involved in nutrient transport and arginine metabolism;and 3)maternal plasma,fetal plasma,allantoic fluid,and amniotic fluid were analyzed for amino acids,agmatine,polyamines,glucose,and fructose.Results:Treatment of ewes with exogenous P4 did not alter fetal or placental growth,but increased amounts of aspartate and arginine in allantoic fluid and amniotic fluid,respectively.Ewes that received exogenous P4 had greater expression of mRNAs for SLC7A1,SLC7A2,SLC2A1,AGMAT,and ODC1 in endometria,as well as SLC1A4,SLC2A5,SLC2A8 and ODC1 in placentomes.In addition,AZIN2 protein was immunolocalized to uterine luminal and glandular epithelia in P4-treated ewes,whereas AZIN2 localized only to uterine luminal epithelia in CO-treated ewes.Conclusions:This study revealed that exogenous P4 administered in early pregnancy influenced expression of selected genes for nutrient transporters and the expression of a protein involved in polyamine synthesis on day 125 of pregnancy,suggesting a‘programming’effect of P4 on gene expression that affected the composition of nutrients in fetal-placental fluids.
文摘Aim: To evaluate the benefits and hazards of routine progesterone supplementation in threatened abortion and whether it is a sound practice or not. Materials and Methods: This study was conducted at Obstetrics and Gynecology Department, Tanta University in the period from January 2018 to December 2018. Eligible patients (n = 190) were randomly allocated into 2 groups: study group who will receive progesterone supplementation (prog. group) and control group who will receive no treatment (place. group). Results: No significant differences were found between both groups regarding all demographic data and pregnancy characteristics. Abortions were higher in place. group 17 (23.94%) than in prog. group 12 (16.44%) with no significant difference p value = 0.263. The incidence of preterm labour was also higher in the place. group 22 (30.99%) in comparison to the prog. group 17 (23.29%) with no significant difference p value = 0.300. Conclusion: Progesterone supplementation in threatened abortion was not beneficial although it reduced abortion and preterm labour rates.
文摘There is currently no standard pharmacological treatment for spinal cord injury. Here, we suggest that progesterone, a steroid hormone, may be a promising therapeutical candidate as it is already for traumatic brain injury, where it has reached phase II clinical trials. We rely on previous works showing anti-inflammatory, neuroprotective and promyelinating roles for progesterone after spinal cord injury and in our recent paper, in which we demonstrate that progesterone diminishes lesion, preserves white matter integrity and improves locomotor recovery in a clinically relevant model of spinal cord lesion.
文摘There are currently no federally approved neuroprotective agents to treat traumatic brain injury. Progesterone, a hydrophobic steroid hormone, has been shown in recent studies to exhibit neu-roprotective effects in controlled cortical impact rat models. Akt is a protein kinase known to play a role in cell signaling pathways that reduce edema, inlfammation, apoptosis, and promote cell growth in the brain. This study aims to determine if progesterone modulates the phosphor-ylation of Aktvia its threonine 308 phosphorylation site. Phosphorylation at the threonine 308 site is one of several sites responsible for activating Akt and enabling the protein kinase to carry out its neuroprotective effects. To assess the effects of progesterone on Akt phosphorylation, C57BL/6 mice were treated with progesterone (8 mg/kg) at 1 (intraperitonally), 6, 24, and 48 hours (subcutaneously) post closed-skull traumatic brain injury. The hippocampus was harvest-ed at 72 hours post injury and prepared for western blot analysis. Traumatic brain injury caused a signiifcant decrease in Akt phosphorylation compared to sham operation. However, mice treat-ed with progesterone following traumatic brain injury had an increase in phosphorylation of Akt compared to traumatic brain injury vehicle. Our ifndings suggest that progesterone is a viable treatment option for activating neuroprotective pathways after traumatic brain injury.
基金Supported by:the Key Construction Program Foundation of Shandong Province during the 11~(th) Five-Year Development Plan Period
文摘BACKGROUND: Coriaria lactone-activated astrocytes released bioactive substances that eventually caused epilepsy. OBJECTIVE: It has been suggested that activated astrocytes alter the expression of the estrogen receptor and progesterone receptor by releasing bioactive substances during epilepsy, thereby affecting neuronal activity in the brain. This study was designed to observe the expression of the estrogen receptor and the progesterone receptor in rat brain following lateral ventricle injection of coriaria lactone-activated, astrocyte-conditioned medium. DESIGN AND SETTING: This immunohistochemical, randomized, controlled, animal study was conducted at the Department of Pathology, Hospital Affiliated to Binzhou Medical College, China. MATERIAL: Coriaria lactone was provided by Huaxi Pharmaceutical Factory, China. METHODS: Forty adult, healthy, male, Sprague Dawley rats were randomly assigned into two groups. Astrocyte-conditioned medium (10 μ L) was injected into rat lateral ventricle in the control group (n = 8). Coriaria lactone-activated, astrocyte-conditioned medium (10 μL) was infused into the rat lateral ventricle in the coriaria lactone group (n = 32). At 2, 4, 8 and 12 hours following injection, rats were sacrificed and subjected to immunohistochemistry. Eight rats were studied at each time point. MAIN OUTCOME MEASURES: Behavioral changes were observed in rats of both groups. Expression of the estrogen receptor and the progesterone receptor in rat cortical and hippocampal neurons was measured using immunohistochemistry. RESULTS: Four hours after injection, estrogen receptor levels in rat cortical and hippocampal neurons were significantly higher in the coriaria lactone group than in the control group (P 〈 0.05). Progesterone receptor levels were significantly lower in the coriaria lactone group than in the control group (P 〈 0.05). Seizures were not observed in the control group. In the coriaria lactone group, convulsions appeared 30 minutes after injection; seizures reached grade Ⅲ at 45 minutes rat behavior was nearly normal at 2 hours. CONCLUSION: Activated astrocytes can induce seizures in the rat by enhancing estrogen receptor expression and decreasing progesterone receptor expression in cerebral cortical and hippocampal neurons.