Objective:To investigate the potential of N-acetylcysteine(NAC)and zinc sulphate(ZnSO_(4))in mitigating reproductive dysfunction caused by di-2-ethylhexyl phthalate(DEHP)in rats and to understand the underlying mechan...Objective:To investigate the potential of N-acetylcysteine(NAC)and zinc sulphate(ZnSO_(4))in mitigating reproductive dysfunction caused by di-2-ethylhexyl phthalate(DEHP)in rats and to understand the underlying mechanisms,specifically oxidative stress and sex hormone receptor activity.Methods:Thirty-five male Wistar rats were randomly divided into five equal groups(n=7 per group).Group 1 was administered 0.5 mL of distilled water and served as the control group.Group 2 was given only DEHP(750 mg/kg/day),while group 3,4 and 5 were given DEHP(750 mg/kg/day)plus NAC(100 mg/kg/day),DEHP(750 mg/kg/day)plus ZnSO_(4)(0.5 mg/kg/day),and DEHP(750 mg/kg/day)plus NAC(100 mg/kg/day)as well as ZnSO_(4)(0.5 mg/kg/day),respectively.All treatments lasted for 21 days.Samples were obtained after the rats were sacrificed,and hormones levels in the serum and markers of oxidative stress in the testicles were analyzed using the enzyme-linked immunosorbent assay.The amount of androgen receptors in the testicles was determined by immunohistochemistry,and the susceptibility of testosterone and DEHP to bind to androgen receptor and 5α-reductase was determined by molecular docking studies.Results:DEHP decreased reproductive hormones,testicular antioxidant enzymes,increased malondialdehyde levels,and negatively impacted histology of the pituitary and testes.NAC or ZnSO_(4) treatment showed a marked improvement in testicular antioxidant status and hormone levels,as well as a positive effect on the histology of the pituitary and testes.The combination of both treatments appeared to be more effective.The affinity of DEHP to bind to androgen receptors may lead to disruption of androgen receptor signaling,which can further result in dysfunction of hormones related to androgen.However,NAC is more likely to form stronger binding interactions with follicle stimulating hormone and luteinizing hormone receptors,as well as gonadotropin-releasing hormone receptors,when compared to DEHP.Conclusions:The possibility that NAC and ZnSO_(4) could downregulate DEHP-induced sex hormone changes is suggested by their potential to reduce toxicity.展开更多
BACKGROUND: Leptin may regulate reproductive function via release of hypothalamic neuropeptide Y. However, it is unknown whether this regulatory effect is limited to the hypothalamus. OBJECTIVE: To detect the effect...BACKGROUND: Leptin may regulate reproductive function via release of hypothalamic neuropeptide Y. However, it is unknown whether this regulatory effect is limited to the hypothalamus. OBJECTIVE: To detect the effect of different dosages of leptin on luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion from in vitro cultured rat anterior pituitary cells. DESIGN: Contrast study based on cells. SETTING: This study was performed in the Basic Institute of Chengde Medical College, Chengde City, Hebei Province, China from March to June 2007. MATERIALS: Eighteen female Wistar rats of three months of age, weighing 200-220 g, and of clean grade were used. Leptin was provided by Peprotech Company, DMEM culture medium by Invitrogen Company, and the radioimmunological kit by Beijing Zhongshan Jinqiao Biotechnology Co., Ltd. METHODS: Three glandular organs were regarded as one group for culture of anterior pituitary cells. In the control group, saline was added to the culture medium instead of leptin. In the leptin group, leptin was prepared into different concentrations of 1×10^-12, 1×10^-11, 1×10^-9, 1×10^-7, and 1×10^-6 mol/L for stimulation of cultured cells. The culture supernatant was obtained at three hours after additional of saline/leptin. MAIN OUTCOME MEASURES: Contents of LH and FSH were detected by radioimmunology. RESULTS: Following leptin stimulation, LH release increased with increasing concentrations of leptin up to 1×10^-9 mol/L, where LH release peaked. LH release then progressively decreased with increasing leptin concentrations (P 〈 0.01). LH release in the leptin (1×10^-12, 1×10^-11, 1×10^-7, and 1×10^-6 mol/L) groups was significantly higher than that in the control group (P 〈 0.01). FSH content in the leptin (1×10^-11, 1×10^-9, and 1×10^-7 mol/L) groups was significantly higher than that in the control group (P 〈 0.01). CONCLUSION: Leptin can directly affect pituitary tissue to promote the secretion of LH and FSH in a dose-dependent manner.展开更多
AIM To investigate the therapeutic potential of two recombinant proteins, Survivin and luteinizing hormone-releasing hormone (LHRH) fusion protein [LHRH(6 leu)-LTB] for immunotherapy of breast cancer.METHODS Murine 4 ...AIM To investigate the therapeutic potential of two recombinant proteins, Survivin and luteinizing hormone-releasing hormone (LHRH) fusion protein [LHRH(6 leu)-LTB] for immunotherapy of breast cancer.METHODS Murine 4 T-1 breast cancer model was used to evaluate the efficacy of recombinant proteins in vivo. Twenty four Balb/c mice were divided into 4 groups of 6 mice each. Recombinant Survivin and LHRH fusion protein, alone or in combination, were administered along with immunomodulator Mycobacterium indicus pranii (MIP) in Balb/c mice. Unimmunized or control group mice were administered with phosphate buffer saline. Each group was then challenged with syngeneic 4 T-1 cells to induce the growth of breast tumor. Tumor growth was monitored to evaluate the efficacy of immune-response in preventing the growth of cancer cells.RESULTS Preventive immunization with 20 μg recombinant Survivin and MIP was effective in suppressing growth of 4 T-1 mouse model of breast cancer (P = 0.04) but 50 μg dose was ineffective in suppressing tumor growth. However, combination of Survivin and LHRH fusion protein was more effective in suppressing tumor growth (P = 0.02) as well as metastasis in vivo in comparison to LHRH fusion protein as vaccine antigen alone.CONCLUSION Recombinant Survivin and MIP suppress tumor growth significantly. Combining LHRH fusion protein with Survivin and MIP enhances tumor suppressive effects marginally which provides evidence for recombinant Survivin and LHRH fusion protein as candidates for translating the combination cancer immunotherapy approaches.展开更多
Aim: To evaluate the long-term effectiveness, side effects and compliance rates of two types of drugs (luteinizing hormone-releasing hormone [LHRH] agonist and antiandrogen) that were used individually to treat pat...Aim: To evaluate the long-term effectiveness, side effects and compliance rates of two types of drugs (luteinizing hormone-releasing hormone [LHRH] agonist and antiandrogen) that were used individually to treat patients with localized prostate cancer (T1-2) at our institution. Methods: Ninety-seven patients who were diagnosed in the period from April 1997 to January 2000 as having clinically localized prostate cancer (T1-2) received either LHRH agonist (leuprolide acetate 7.5 mg/month) monotherapy (group 1, n = 62) or antiandrogen monotherapy (group 2, n = 35; 18 received bicalutamide 50 mg q.d., 13 received nilutamide 150 mg t.i.d, and 4 received flutamide 250 mg t.i.d.). The mean age in both groups was 76 years. Results: The mean follow-up time was (50.8 ±8.5) months in group 1 and (43.1 ± 2.2) months in group 2. Prostate-specific antigen (PSA) levels rose in only 1 of the 62 patients (1.6%) in group 1, and in 20 of the 35 patients (57.1%) in group 2. In group 2, 10 of the 20 patients (50 %) with increasing PSA levels were treated with LHRH salvage therapy, and eight (80%) responded. Hot flashes (54.8%) and lethargy (41.9%) were the most common side effects in group 1. In contrast, nipple-tenderness (40%) and light-dark adaptation (17.1%) were more often seen in group 2. Only 1 of the 62 patients (1.6%) in group 1 switched to another medication because of adverse side effects; whereas 8 of the 35 patients (22.9%) in group 2 did so. Conclusion: Unlike antiandrogen monotherapy, LHRH agonist monotherapy provided long-term durable control of localized prostate cancer (T1-2). It can also be an effective treatment option for patients whose disease failed to respond to antiandrogen monotherapy. The limitations of our study are the lack of health outcomes analysis and a small sample size.展开更多
Luteinizing hormone-releasing hormone(LHRH) is known to influence sexual behavior in many vertebrate taxa, but there have been no systematic studies on the role of LHRH in sexual behavior of turtles. We tested the hyp...Luteinizing hormone-releasing hormone(LHRH) is known to influence sexual behavior in many vertebrate taxa, but there have been no systematic studies on the role of LHRH in sexual behavior of turtles. We tested the hypotheses that exogenous LHRH analogues would induce sexual behavior of male Four-eyed turtle, Sacalia quadriocellata. We examined this by challenging males with intramuscular injections of mammalian luteinizing hormone-releasing hormone analogue(LHRH-A), human chorionic gonadotropin(HCG), or a combination of the two, and subsequently exposing them to sexually receptive females for behavioral observation. Our data show that the injection of only HCG could not, while that of only LHRH-A could, facilitate sexual behavior along with testicular recrudescence and spermatogenesis in S. quadriocellata. The injection of both LHRH-A and HCG would induce more drastic sexual behavior of the animals than that of LHRH-A alone, indicating HCG enhances the effects of LHRH-A induced sexual behavior. However, different pharmacological dosages of LHRH-A(0.5 μg, 1 μg, 2 μg per 100 g bodyweight) did not correspond to different activity levels. Though the mechanism of LHRH effect was not determined, this study may support that the sexual behavior of S. quadriocellata which occurs at the beginning of the injection despite regression of the gonads. This is the first report on the exogenous LHRH-A induced sexual behavior for this species.展开更多
Objective To identify the morphological characteristics of pituitary luteinizing hormone (LH) cells after exogenous gonadal hormone treatment Methods Effects of various doses of estrogen, progesterone and their...Objective To identify the morphological characteristics of pituitary luteinizing hormone (LH) cells after exogenous gonadal hormone treatment Methods Effects of various doses of estrogen, progesterone and their combination on morphological parameters, including the size and shape of pituitary LH cells, the size of endocellular vacuoles, were observed and measured by immuno histochemistry and computer image analysis. Results Different kinds of gonadal hormones could recover the magnified LH cells to the normal level in ovariectomized rats. However, their final effects on the gonadotrophin levels and the cellular morphological characters of the LH cells were different. The low dose of estrogen elicited abundant hormone stored in the LH cells to an easy released status with a lot of different size of vacuoles. On the contrary, the high dose of estrogen inhibited the storage of LH, and the LH cells were filled with secretory granules and few vacuoles. The progesterone could promote the storage of LH in an uneasy released status. The administration of estrogen progesterone combination not only inhibited the storage of LH, but also the release of LH. In this group, the LH cells containing a large amount of secretory granules and a few vacuoles showed a better uniform shape compared with those administrated with high dose of estrogen. Conclusion: Different kinds of gonadal hormones could reverse the excessive secretion of LH and recover the morphological change of LH cells to the normally physiological condition.展开更多
Background:Replacement gilts are typically fed ad libitum,whereas emerging evidence from human and rodent studies has revealed that time-restricted access to food has health benefits.The objective of this study was to...Background:Replacement gilts are typically fed ad libitum,whereas emerging evidence from human and rodent studies has revealed that time-restricted access to food has health benefits.The objective of this study was to investigate the effect of meal frequency on the metabolic status and ovarian follicular development in gilts.Methods:A total of 36 gilts(Landrace×Yorkshire)with an age of 150±3 d and a body weight of 77.6±3.8 kg were randomly allocated into one of three groups(n=12 in each group),and based on the group allocation,the gilts were fed at a frequency of one meal(T1),two meals(T2),or six meals per day(T6)for 14 consecutive weeks.The effects of the meal frequency on growth preference,nutrient utilization,short-chain fatty acid production by gut microbial,the post-meal dynamics in the metabolic status,reproductive hormone secretions,and ovarian follicular development in the gilts were measured.Results:The gilts in the T1 group presented a higher average daily gain(+48 g/d,P<0.05)and a higher body weight(+4.9 kg,P<0.05)than those in the T6 group.The meal frequency had no effect on the apparent digestibility of dry matter,crude protein,ether extract,ash,and gross energy,with the exception that the T1 gilts exhibited a greater NDF digestibility than the T6 gilts(P<0.05).The nitrogen balance analysis revealed that the T1 gilts presented decreased urine excretion of nitrogen(−8.17 g/d,P<0.05)and higher nitrogen retention(+9.81 g/d,P<0.05),and thus exhibited higher nitrogen utilization than the T6 gilts.The time-course dynamics of glucose,α-amino nitrogen,urea,lactate,and insulin levels in serum revealed that the T1 group exhibited higher utilization of nutrients after a meal than the T2 or T6 gilts.The T1 gilts also had a higher acetate content and SCFAs in feces than the T6 gilts(P<0.05).The age,body weight and backfat thickness of the gilts at first estrous expression were not affected by the meal frequency,but the gilts in the T1 group had higher levels of serum luteinizing hormone on the 18th day of the 3rd estrus cycle and 17β-estradiol,a larger number of growing follicles and corpora lutea,and higher mRNA expression levels of genes related to follicular development on the 19th day of the 3rd estrus cycle.Conclusions:The current findings revealed the benefits of a lower meal frequency equal feed intake on nutrient utilization and reproductive function in replacement gilts,and thus provide new insights into the nutritional strategy for replacement gilts,and the dietary pattern for other mammals,such as humans.展开更多
Aim: In the testicular capsulotomized rats, although there was a significant increase in the luteinizing hormone (LH)levels, the secretion of testosterone remained low. In order to clarify the mechanisms of this pheno...Aim: In the testicular capsulotomized rats, although there was a significant increase in the luteinizing hormone (LH)levels, the secretion of testosterone remained low. In order to clarify the mechanisms of this phenomenon, the bindingof endogenous LH to the testes were observed before and after testicular capsulotomy. Methods; Peroxidase-anti-peroxidase (PAP) method was used to detect the binding of LH to the testes in rats. Results; An intense positivestaining of LH was found in the Leydig cells of both the normal and sham-operated control testes. However, at 40 d af-ter operation, the LH immunoreactivity was decreased in the Leydig cells of the capsulotomized testis. By d 60, onlyvery weak positive staining could be observed in these cells. Conclusion; A progressive reduction of endogenousLH binding to the testis occurred in the capsulotomized rat. (Asian J Androl 2001 Sep; 3 : 227 - 230)展开更多
Kisspeptin (KP) , a neuroendocrine regulator of reproduction,is hypothesized to be an integrator of metabolism and hormones critical to the regulation of reproduction. Lactation is associated with enhanced growth ho...Kisspeptin (KP) , a neuroendocrine regulator of reproduction,is hypothesized to be an integrator of metabolism and hormones critical to the regulation of reproduction. Lactation is associated with enhanced growth hormone (GH) responsiveness and reduced fertility. Our study was designed to determine the effects of lactation on KP-stimulated GH and luteinizing hormone (LH) secretion. Five non-lactating and five lactating dairy cows were used in the study. Experiments were conducted with lactating cows at weeks 1,5 and 11 after parturition. The experimental treatments (saline and KP [100 and 400 pmol / kg body weight]) were given intravenously and blood was collected and plasma was stored until later assay to determine concentrations of GH,LH,progesterone and nonesterified fatty acids. We found that neither dose of KP stimulated an increase in GH secretion. The low dose ofKP increased (P 〈0. 05) LH concentrations only in lactating cows. The higher dose of KP elicited an increase in circulating LH concentrations in both lactating and non-lactating cows. The lower dose of KP increased (P 〈 0. 05) the area under the curve for LH only in cows during week 5 of lactation,and the area under the curve of LH following the highest dose of KP was greater (P 〈 0. 05) in cows during week 5 of lactation than that for the other groups of cows. In summary,lactation status and stage of lactation did not change the sensitivity of the GH system to KP. However,an effect of stage of lactation on KP-stimulated LH secretion was detected in the dairy cows. Study of the KP system during lactation in dairy cows may provide critical insights into the mechanisms for lactation-associated changes in the reproductive axis.展开更多
The reproductive behaviors of birds are mainly controlled by the hypothalamus-pituitary-gonad axis.Many studies have shown that reproductive hormones are tightly linked to the breeding sub-stages.However,only a few st...The reproductive behaviors of birds are mainly controlled by the hypothalamus-pituitary-gonad axis.Many studies have shown that reproductive hormones are tightly linked to the breeding sub-stages.However,only a few studies have examined the temporal trend of hormone levels among different reproductive stages in multiple brooded species.We investigated the changes in plasma luteinizing hormone(LH)and prolactin(PRL)concentrations during different reproductive stages of the facultative double-brooded Great Tit(Parus major).We found that the concentrations of LH and PRL in females were significantly higher than those in males.Females had significantly higher LH and lower PRL concentrations in the pre-breeding period than in the first/second brooding periods,and there were no significant changes between the first and second brooding periods.The concentrations of LH and PRL in males had no significant difference between the pre-breeding period and the first brooding periods,while LH and PRL concentrations in the second brooding period were significantly higher than those in the first brooding period.We conclude that there are sex-based differences between LH and PRL at different stages of reproduction.The changes in LH and PRL in both males and females should be related to their physiological functions.Especially for males,individuals with higher levels of LH and PRL are more likely to maintain second clutches.展开更多
Objective:Optimal luteinizing hormone(LH)levels forin vitro fertilization/intracytoplasmic sperm injection(IVF/ICSI)patients following the gonadotropin-releasing hormone(GnRH)antagonist protocol remain controversial.T...Objective:Optimal luteinizing hormone(LH)levels forin vitro fertilization/intracytoplasmic sperm injection(IVF/ICSI)patients following the gonadotropin-releasing hormone(GnRH)antagonist protocol remain controversial.This study aimed to estimate the association between serum LH levels on the triggering day(LHLOT)and clinical pregnancy outcomes in IVF/ICSI patients following the GnRH antagonist protocol.Methods:We enrolled 4743 IVF/ICSI cycles using flexible or fixed GnRH antagonist protocols between January 2017 and June 2021.The patients were stratified into four groups according to the LHLOT quartiles(Q1–Q4).Each group was further divided into two subgroups according to the median basal LH/LHLOT.The main outcomes were clinical pregnancy,birth,and miscarriage rates.Secondary outcomes were oocyte yield,number of MII,fertilized oocytes(2PN),and high-quality embryos.Results:Serum LHLOT levels were negatively correlated with oocyte yield and the numbers of MII,2PN,and high-quality embryos.Reproductive outcomes were compared among the different quartiles and subgroups.The absolute difference in the clinical pregnancy rates between the Q4 and Q1 groups was 6.4%(47.2%vs.40.8%,P<0.05).Clinical pregnancy rates between the subgroups with basal LH/LHLOT>3.04 and≤3.04 were 32.7%and 48.6%(P<0.01),respectively,in Q1.Within Q3,the clinical pregnancy rates between the subgroups with basal LH/LHLOT>2.14 and≤2.14 were 50.2%and 41.9%,respectively(P<0.05).The greater the decrease in LH levels,the lower the oocyte maturation rate across all quartiles.Conclusions:According to the LHLOT quartiles,the Q1 of serum LHLOT<1.43 IU/L may result in a higher number of oocytes but reduced oocyte maturation and lower clinical pregnancy rates.A decrease in LH levels by approximately 2.14 to 3.04 times compared to basal LH levels may lead to higher clinical pregnancy rates in IVF/ICSI patients following the GnRH antagonist protocol.展开更多
Background: The pathologies causing male infertility are various (congenital or acquired) and concern several hormone-producing organs: the hypothalamus, pituitary gland, testes and adrenals. The hormonal dosage inclu...Background: The pathologies causing male infertility are various (congenital or acquired) and concern several hormone-producing organs: the hypothalamus, pituitary gland, testes and adrenals. The hormonal dosage includes systematically testosterone, FSH and LH. These analyses often highlight hypogonadism hypogonadotropic or hypergonadotropic. They can sometimes be normal. The present study aimed to establish the hormonal profile of infertile men residing in Brazzaville. Patients and Methods: It was a cross-sectional descriptive study during five years (from 2018 to 2023). It concerned 344 infertilemen with an abnormal spermogram and spermocytogram. The method was performed from the blood dosage of testosterone, FSH, and LH using the Elisa technique. Results: The hormonal assessment was not normal in 48.83% (168/344) of cases. Increased values of testosterone were noted in 6.10% of cases and decreased in 12.20%. Abnormal high values of FSH were observed in 14.24% of cases and decreased values in 8.13%. LH was elevated, i.e. 2.03% of cases and decreased in 6.10% of subjects. Conclusions: A hormonal disturbance was observed in almost half of the infertile men. It concerned the hypothalamus-pituitary and the testes axis and indicated mainly a state of hypogonadism with high FSH and low LH.展开更多
文摘Objective:To investigate the potential of N-acetylcysteine(NAC)and zinc sulphate(ZnSO_(4))in mitigating reproductive dysfunction caused by di-2-ethylhexyl phthalate(DEHP)in rats and to understand the underlying mechanisms,specifically oxidative stress and sex hormone receptor activity.Methods:Thirty-five male Wistar rats were randomly divided into five equal groups(n=7 per group).Group 1 was administered 0.5 mL of distilled water and served as the control group.Group 2 was given only DEHP(750 mg/kg/day),while group 3,4 and 5 were given DEHP(750 mg/kg/day)plus NAC(100 mg/kg/day),DEHP(750 mg/kg/day)plus ZnSO_(4)(0.5 mg/kg/day),and DEHP(750 mg/kg/day)plus NAC(100 mg/kg/day)as well as ZnSO_(4)(0.5 mg/kg/day),respectively.All treatments lasted for 21 days.Samples were obtained after the rats were sacrificed,and hormones levels in the serum and markers of oxidative stress in the testicles were analyzed using the enzyme-linked immunosorbent assay.The amount of androgen receptors in the testicles was determined by immunohistochemistry,and the susceptibility of testosterone and DEHP to bind to androgen receptor and 5α-reductase was determined by molecular docking studies.Results:DEHP decreased reproductive hormones,testicular antioxidant enzymes,increased malondialdehyde levels,and negatively impacted histology of the pituitary and testes.NAC or ZnSO_(4) treatment showed a marked improvement in testicular antioxidant status and hormone levels,as well as a positive effect on the histology of the pituitary and testes.The combination of both treatments appeared to be more effective.The affinity of DEHP to bind to androgen receptors may lead to disruption of androgen receptor signaling,which can further result in dysfunction of hormones related to androgen.However,NAC is more likely to form stronger binding interactions with follicle stimulating hormone and luteinizing hormone receptors,as well as gonadotropin-releasing hormone receptors,when compared to DEHP.Conclusions:The possibility that NAC and ZnSO_(4) could downregulate DEHP-induced sex hormone changes is suggested by their potential to reduce toxicity.
文摘BACKGROUND: Leptin may regulate reproductive function via release of hypothalamic neuropeptide Y. However, it is unknown whether this regulatory effect is limited to the hypothalamus. OBJECTIVE: To detect the effect of different dosages of leptin on luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion from in vitro cultured rat anterior pituitary cells. DESIGN: Contrast study based on cells. SETTING: This study was performed in the Basic Institute of Chengde Medical College, Chengde City, Hebei Province, China from March to June 2007. MATERIALS: Eighteen female Wistar rats of three months of age, weighing 200-220 g, and of clean grade were used. Leptin was provided by Peprotech Company, DMEM culture medium by Invitrogen Company, and the radioimmunological kit by Beijing Zhongshan Jinqiao Biotechnology Co., Ltd. METHODS: Three glandular organs were regarded as one group for culture of anterior pituitary cells. In the control group, saline was added to the culture medium instead of leptin. In the leptin group, leptin was prepared into different concentrations of 1×10^-12, 1×10^-11, 1×10^-9, 1×10^-7, and 1×10^-6 mol/L for stimulation of cultured cells. The culture supernatant was obtained at three hours after additional of saline/leptin. MAIN OUTCOME MEASURES: Contents of LH and FSH were detected by radioimmunology. RESULTS: Following leptin stimulation, LH release increased with increasing concentrations of leptin up to 1×10^-9 mol/L, where LH release peaked. LH release then progressively decreased with increasing leptin concentrations (P 〈 0.01). LH release in the leptin (1×10^-12, 1×10^-11, 1×10^-7, and 1×10^-6 mol/L) groups was significantly higher than that in the control group (P 〈 0.01). FSH content in the leptin (1×10^-11, 1×10^-9, and 1×10^-7 mol/L) groups was significantly higher than that in the control group (P 〈 0.01). CONCLUSION: Leptin can directly affect pituitary tissue to promote the secretion of LH and FSH in a dose-dependent manner.
文摘AIM To investigate the therapeutic potential of two recombinant proteins, Survivin and luteinizing hormone-releasing hormone (LHRH) fusion protein [LHRH(6 leu)-LTB] for immunotherapy of breast cancer.METHODS Murine 4 T-1 breast cancer model was used to evaluate the efficacy of recombinant proteins in vivo. Twenty four Balb/c mice were divided into 4 groups of 6 mice each. Recombinant Survivin and LHRH fusion protein, alone or in combination, were administered along with immunomodulator Mycobacterium indicus pranii (MIP) in Balb/c mice. Unimmunized or control group mice were administered with phosphate buffer saline. Each group was then challenged with syngeneic 4 T-1 cells to induce the growth of breast tumor. Tumor growth was monitored to evaluate the efficacy of immune-response in preventing the growth of cancer cells.RESULTS Preventive immunization with 20 μg recombinant Survivin and MIP was effective in suppressing growth of 4 T-1 mouse model of breast cancer (P = 0.04) but 50 μg dose was ineffective in suppressing tumor growth. However, combination of Survivin and LHRH fusion protein was more effective in suppressing tumor growth (P = 0.02) as well as metastasis in vivo in comparison to LHRH fusion protein as vaccine antigen alone.CONCLUSION Recombinant Survivin and MIP suppress tumor growth significantly. Combining LHRH fusion protein with Survivin and MIP enhances tumor suppressive effects marginally which provides evidence for recombinant Survivin and LHRH fusion protein as candidates for translating the combination cancer immunotherapy approaches.
文摘Aim: To evaluate the long-term effectiveness, side effects and compliance rates of two types of drugs (luteinizing hormone-releasing hormone [LHRH] agonist and antiandrogen) that were used individually to treat patients with localized prostate cancer (T1-2) at our institution. Methods: Ninety-seven patients who were diagnosed in the period from April 1997 to January 2000 as having clinically localized prostate cancer (T1-2) received either LHRH agonist (leuprolide acetate 7.5 mg/month) monotherapy (group 1, n = 62) or antiandrogen monotherapy (group 2, n = 35; 18 received bicalutamide 50 mg q.d., 13 received nilutamide 150 mg t.i.d, and 4 received flutamide 250 mg t.i.d.). The mean age in both groups was 76 years. Results: The mean follow-up time was (50.8 ±8.5) months in group 1 and (43.1 ± 2.2) months in group 2. Prostate-specific antigen (PSA) levels rose in only 1 of the 62 patients (1.6%) in group 1, and in 20 of the 35 patients (57.1%) in group 2. In group 2, 10 of the 20 patients (50 %) with increasing PSA levels were treated with LHRH salvage therapy, and eight (80%) responded. Hot flashes (54.8%) and lethargy (41.9%) were the most common side effects in group 1. In contrast, nipple-tenderness (40%) and light-dark adaptation (17.1%) were more often seen in group 2. Only 1 of the 62 patients (1.6%) in group 1 switched to another medication because of adverse side effects; whereas 8 of the 35 patients (22.9%) in group 2 did so. Conclusion: Unlike antiandrogen monotherapy, LHRH agonist monotherapy provided long-term durable control of localized prostate cancer (T1-2). It can also be an effective treatment option for patients whose disease failed to respond to antiandrogen monotherapy. The limitations of our study are the lack of health outcomes analysis and a small sample size.
基金supported by the National Natural Science Foundation of China(30910103916)the Key Project of the Science and Technology Program of Hainan,China(06122)
文摘Luteinizing hormone-releasing hormone(LHRH) is known to influence sexual behavior in many vertebrate taxa, but there have been no systematic studies on the role of LHRH in sexual behavior of turtles. We tested the hypotheses that exogenous LHRH analogues would induce sexual behavior of male Four-eyed turtle, Sacalia quadriocellata. We examined this by challenging males with intramuscular injections of mammalian luteinizing hormone-releasing hormone analogue(LHRH-A), human chorionic gonadotropin(HCG), or a combination of the two, and subsequently exposing them to sexually receptive females for behavioral observation. Our data show that the injection of only HCG could not, while that of only LHRH-A could, facilitate sexual behavior along with testicular recrudescence and spermatogenesis in S. quadriocellata. The injection of both LHRH-A and HCG would induce more drastic sexual behavior of the animals than that of LHRH-A alone, indicating HCG enhances the effects of LHRH-A induced sexual behavior. However, different pharmacological dosages of LHRH-A(0.5 μg, 1 μg, 2 μg per 100 g bodyweight) did not correspond to different activity levels. Though the mechanism of LHRH effect was not determined, this study may support that the sexual behavior of S. quadriocellata which occurs at the beginning of the injection despite regression of the gonads. This is the first report on the exogenous LHRH-A induced sexual behavior for this species.
基金the National Key L aboratory of Contraceptive Drugs and Device( No.B2 -97-8) and the National Natural Science Foundation of China( No.3 9670 3 1 3 )
文摘Objective To identify the morphological characteristics of pituitary luteinizing hormone (LH) cells after exogenous gonadal hormone treatment Methods Effects of various doses of estrogen, progesterone and their combination on morphological parameters, including the size and shape of pituitary LH cells, the size of endocellular vacuoles, were observed and measured by immuno histochemistry and computer image analysis. Results Different kinds of gonadal hormones could recover the magnified LH cells to the normal level in ovariectomized rats. However, their final effects on the gonadotrophin levels and the cellular morphological characters of the LH cells were different. The low dose of estrogen elicited abundant hormone stored in the LH cells to an easy released status with a lot of different size of vacuoles. On the contrary, the high dose of estrogen inhibited the storage of LH, and the LH cells were filled with secretory granules and few vacuoles. The progesterone could promote the storage of LH in an uneasy released status. The administration of estrogen progesterone combination not only inhibited the storage of LH, but also the release of LH. In this group, the LH cells containing a large amount of secretory granules and a few vacuoles showed a better uniform shape compared with those administrated with high dose of estrogen. Conclusion: Different kinds of gonadal hormones could reverse the excessive secretion of LH and recover the morphological change of LH cells to the normally physiological condition.
基金This study was supported by National Key R&D Program of China(2018YFD0501005)National Natural Science Foundation of China,PR China(31772616).
文摘Background:Replacement gilts are typically fed ad libitum,whereas emerging evidence from human and rodent studies has revealed that time-restricted access to food has health benefits.The objective of this study was to investigate the effect of meal frequency on the metabolic status and ovarian follicular development in gilts.Methods:A total of 36 gilts(Landrace×Yorkshire)with an age of 150±3 d and a body weight of 77.6±3.8 kg were randomly allocated into one of three groups(n=12 in each group),and based on the group allocation,the gilts were fed at a frequency of one meal(T1),two meals(T2),or six meals per day(T6)for 14 consecutive weeks.The effects of the meal frequency on growth preference,nutrient utilization,short-chain fatty acid production by gut microbial,the post-meal dynamics in the metabolic status,reproductive hormone secretions,and ovarian follicular development in the gilts were measured.Results:The gilts in the T1 group presented a higher average daily gain(+48 g/d,P<0.05)and a higher body weight(+4.9 kg,P<0.05)than those in the T6 group.The meal frequency had no effect on the apparent digestibility of dry matter,crude protein,ether extract,ash,and gross energy,with the exception that the T1 gilts exhibited a greater NDF digestibility than the T6 gilts(P<0.05).The nitrogen balance analysis revealed that the T1 gilts presented decreased urine excretion of nitrogen(−8.17 g/d,P<0.05)and higher nitrogen retention(+9.81 g/d,P<0.05),and thus exhibited higher nitrogen utilization than the T6 gilts.The time-course dynamics of glucose,α-amino nitrogen,urea,lactate,and insulin levels in serum revealed that the T1 group exhibited higher utilization of nutrients after a meal than the T2 or T6 gilts.The T1 gilts also had a higher acetate content and SCFAs in feces than the T6 gilts(P<0.05).The age,body weight and backfat thickness of the gilts at first estrous expression were not affected by the meal frequency,but the gilts in the T1 group had higher levels of serum luteinizing hormone on the 18th day of the 3rd estrus cycle and 17β-estradiol,a larger number of growing follicles and corpora lutea,and higher mRNA expression levels of genes related to follicular development on the 19th day of the 3rd estrus cycle.Conclusions:The current findings revealed the benefits of a lower meal frequency equal feed intake on nutrient utilization and reproductive function in replacement gilts,and thus provide new insights into the nutritional strategy for replacement gilts,and the dietary pattern for other mammals,such as humans.
文摘Aim: In the testicular capsulotomized rats, although there was a significant increase in the luteinizing hormone (LH)levels, the secretion of testosterone remained low. In order to clarify the mechanisms of this phenomenon, the bindingof endogenous LH to the testes were observed before and after testicular capsulotomy. Methods; Peroxidase-anti-peroxidase (PAP) method was used to detect the binding of LH to the testes in rats. Results; An intense positivestaining of LH was found in the Leydig cells of both the normal and sham-operated control testes. However, at 40 d af-ter operation, the LH immunoreactivity was decreased in the Leydig cells of the capsulotomized testis. By d 60, onlyvery weak positive staining could be observed in these cells. Conclusion; A progressive reduction of endogenousLH binding to the testis occurred in the capsulotomized rat. (Asian J Androl 2001 Sep; 3 : 227 - 230)
基金an Animal Health and Disease Research grant from the College of Veterinary Medicine at Auburn University (Auburn,AL)supported by an Agricultural and Food Research Initiative Competitive grant no. 2010-6520620647 from the USDA National Institute of Food and Agriculture
文摘Kisspeptin (KP) , a neuroendocrine regulator of reproduction,is hypothesized to be an integrator of metabolism and hormones critical to the regulation of reproduction. Lactation is associated with enhanced growth hormone (GH) responsiveness and reduced fertility. Our study was designed to determine the effects of lactation on KP-stimulated GH and luteinizing hormone (LH) secretion. Five non-lactating and five lactating dairy cows were used in the study. Experiments were conducted with lactating cows at weeks 1,5 and 11 after parturition. The experimental treatments (saline and KP [100 and 400 pmol / kg body weight]) were given intravenously and blood was collected and plasma was stored until later assay to determine concentrations of GH,LH,progesterone and nonesterified fatty acids. We found that neither dose of KP stimulated an increase in GH secretion. The low dose ofKP increased (P 〈0. 05) LH concentrations only in lactating cows. The higher dose of KP elicited an increase in circulating LH concentrations in both lactating and non-lactating cows. The lower dose of KP increased (P 〈 0. 05) the area under the curve for LH only in cows during week 5 of lactation,and the area under the curve of LH following the highest dose of KP was greater (P 〈 0. 05) in cows during week 5 of lactation than that for the other groups of cows. In summary,lactation status and stage of lactation did not change the sensitivity of the GH system to KP. However,an effect of stage of lactation on KP-stimulated LH secretion was detected in the dairy cows. Study of the KP system during lactation in dairy cows may provide critical insights into the mechanisms for lactation-associated changes in the reproductive axis.
基金supported by the National Natural Science Foundation of China (No.31770419 and 31971402 to HW,32001094 and 31870368 to JY)
文摘The reproductive behaviors of birds are mainly controlled by the hypothalamus-pituitary-gonad axis.Many studies have shown that reproductive hormones are tightly linked to the breeding sub-stages.However,only a few studies have examined the temporal trend of hormone levels among different reproductive stages in multiple brooded species.We investigated the changes in plasma luteinizing hormone(LH)and prolactin(PRL)concentrations during different reproductive stages of the facultative double-brooded Great Tit(Parus major).We found that the concentrations of LH and PRL in females were significantly higher than those in males.Females had significantly higher LH and lower PRL concentrations in the pre-breeding period than in the first/second brooding periods,and there were no significant changes between the first and second brooding periods.The concentrations of LH and PRL in males had no significant difference between the pre-breeding period and the first brooding periods,while LH and PRL concentrations in the second brooding period were significantly higher than those in the first brooding period.We conclude that there are sex-based differences between LH and PRL at different stages of reproduction.The changes in LH and PRL in both males and females should be related to their physiological functions.Especially for males,individuals with higher levels of LH and PRL are more likely to maintain second clutches.
基金National Key R&D Program of China(2018YFC1003200)Natural Science Foundation of China(81873819)+2 种基金National Natural Science Foundation of China(82101759)Zhejiang Provincial Natural Science Foundation of China(LQ22H040006)Zhejiang Provincial Science and Technology Project of China(2021C03100)。
文摘Objective:Optimal luteinizing hormone(LH)levels forin vitro fertilization/intracytoplasmic sperm injection(IVF/ICSI)patients following the gonadotropin-releasing hormone(GnRH)antagonist protocol remain controversial.This study aimed to estimate the association between serum LH levels on the triggering day(LHLOT)and clinical pregnancy outcomes in IVF/ICSI patients following the GnRH antagonist protocol.Methods:We enrolled 4743 IVF/ICSI cycles using flexible or fixed GnRH antagonist protocols between January 2017 and June 2021.The patients were stratified into four groups according to the LHLOT quartiles(Q1–Q4).Each group was further divided into two subgroups according to the median basal LH/LHLOT.The main outcomes were clinical pregnancy,birth,and miscarriage rates.Secondary outcomes were oocyte yield,number of MII,fertilized oocytes(2PN),and high-quality embryos.Results:Serum LHLOT levels were negatively correlated with oocyte yield and the numbers of MII,2PN,and high-quality embryos.Reproductive outcomes were compared among the different quartiles and subgroups.The absolute difference in the clinical pregnancy rates between the Q4 and Q1 groups was 6.4%(47.2%vs.40.8%,P<0.05).Clinical pregnancy rates between the subgroups with basal LH/LHLOT>3.04 and≤3.04 were 32.7%and 48.6%(P<0.01),respectively,in Q1.Within Q3,the clinical pregnancy rates between the subgroups with basal LH/LHLOT>2.14 and≤2.14 were 50.2%and 41.9%,respectively(P<0.05).The greater the decrease in LH levels,the lower the oocyte maturation rate across all quartiles.Conclusions:According to the LHLOT quartiles,the Q1 of serum LHLOT<1.43 IU/L may result in a higher number of oocytes but reduced oocyte maturation and lower clinical pregnancy rates.A decrease in LH levels by approximately 2.14 to 3.04 times compared to basal LH levels may lead to higher clinical pregnancy rates in IVF/ICSI patients following the GnRH antagonist protocol.
文摘Background: The pathologies causing male infertility are various (congenital or acquired) and concern several hormone-producing organs: the hypothalamus, pituitary gland, testes and adrenals. The hormonal dosage includes systematically testosterone, FSH and LH. These analyses often highlight hypogonadism hypogonadotropic or hypergonadotropic. They can sometimes be normal. The present study aimed to establish the hormonal profile of infertile men residing in Brazzaville. Patients and Methods: It was a cross-sectional descriptive study during five years (from 2018 to 2023). It concerned 344 infertilemen with an abnormal spermogram and spermocytogram. The method was performed from the blood dosage of testosterone, FSH, and LH using the Elisa technique. Results: The hormonal assessment was not normal in 48.83% (168/344) of cases. Increased values of testosterone were noted in 6.10% of cases and decreased in 12.20%. Abnormal high values of FSH were observed in 14.24% of cases and decreased values in 8.13%. LH was elevated, i.e. 2.03% of cases and decreased in 6.10% of subjects. Conclusions: A hormonal disturbance was observed in almost half of the infertile men. It concerned the hypothalamus-pituitary and the testes axis and indicated mainly a state of hypogonadism with high FSH and low LH.