Recent studies have revealed that lipid droplets accumulate in neurons after brain injury and evoke lipotoxicity,damaging the neurons.However,how lipids are metabolized by spinal cord neurons after spinal cord injury ...Recent studies have revealed that lipid droplets accumulate in neurons after brain injury and evoke lipotoxicity,damaging the neurons.However,how lipids are metabolized by spinal cord neurons after spinal cord injury remains unclear.Herein,we investigated lipid metabolism by spinal cord neurons after spinal cord injury and identified lipid-lowering compounds to treat spinal cord injury.We found that lipid droplets accumulated in perilesional spinal cord neurons after spinal cord injury in mice.Lipid droplet accumulation could be induced by myelin debris in HT22 cells.Myelin debris degradation by phospholipase led to massive free fatty acid production,which increased lipid droplet synthesis,β-oxidation,and oxidative phosphorylation.Excessive oxidative phosphorylation increased reactive oxygen species generation,which led to increased lipid peroxidation and HT22 cell apoptosis.Bromocriptine was identified as a lipid-lowering compound that inhibited phosphorylation of cytosolic phospholipase A2 by reducing the phosphorylation of extracellular signal-regulated kinases 1/2 in the mitogen-activated protein kinase pathway,thereby inhibiting myelin debris degradation by cytosolic phospholipase A2 and alleviating lipid droplet accumulation in myelin debris-treated HT22 cells.Motor function,lipid droplet accumulation in spinal cord neurons and neuronal survival were all improved in bromocriptine-treated mice after spinal cord injury.The results suggest that bromocriptine can protect neurons from lipotoxic damage after spinal cord injury via the extracellular signal-regulated kinases 1/2-cytosolic phospholipase A2 pathway.展开更多
Dopamine agonists effectively reduce the secretion of prolactin (PRL) in the great majority of prolactinomas and reduce the bulk of the adenomas, as well as have partial therapeutic effect on some patients with acrome...Dopamine agonists effectively reduce the secretion of prolactin (PRL) in the great majority of prolactinomas and reduce the bulk of the adenomas, as well as have partial therapeutic effect on some patients with acromegaly. The inhibitory effect of bromocriptine (BC), a dopamine agonist, on growth hormone (GH) and PRL secretion of dispersed cells from the pituitary adenomas of 16 cases of acromegaly, which secret GH and PRL simultaneously, were evaluated in vitro. The significant inhibitory effects of BC on PRL secretion were found in 12 cases. It was also found that PRL secretion was strongly inhibited when GH was suppressed; on the contrary, when GH secretion was not suppressed, the production of PRL was not or weakly inhibited. The exact mechanism of the effects is nuclear so far. It is necessary to investigate, at molecular level, the etiology of GH-PRL adenomas and its response to therapeutic agents.展开更多
BACKGROUND Some patients present to the intensive care unit due to noninfectious pathologies resulting in fever,especially acute neurological injuries,including brain trauma and intracranial haemorrhage.The cause has ...BACKGROUND Some patients present to the intensive care unit due to noninfectious pathologies resulting in fever,especially acute neurological injuries,including brain trauma and intracranial haemorrhage.The cause has been identified to be central hyperthermia characterized by a high core temperature and a poor response to antipyretics and antibiotics.However,no proper guidelines on how to treat central hyperthermia have been developed for clinical practice.CASE SUMMARY A 63-year-old woman was transferred to our hospital due to injury after a traffic accident.Eight hours after admission,her pupils enlarged bilaterally from 2.5 mm to 4.0 mm.She developed severe coma and underwent decompressive craniectomy.She was diagnosed with central hyperthermia after surgery and was prescribed bromocriptine.The standard dose of bromocriptine could not control her hyperpyrexia,and we prescribed 30 mg a day to control her temperature.CONCLUSION Bromocriptine may be effective in controlling central hyperthermia and have a dosage effect.展开更多
Strong evidence showed that fever after traumatic brain injury TBI is associated with increased mortality. In this study, we tried to evaluate the role of Bromocriptine in central hyperthermia in patients with severe ...Strong evidence showed that fever after traumatic brain injury TBI is associated with increased mortality. In this study, we tried to evaluate the role of Bromocriptine in central hyperthermia in patients with severe TBI. This prospective controlled study was conducted on 50 severe TBI patients who admitted to the critical care department and confirmed on Computed Tomography (CT) of the brain and GCS of less than 9 at admission. Then, they were randomly assigned into 2 groups. Bromocriptine group (25) received bromocriptine 7.5 mg/day during 24 hours from admission through a naso-gastric (NG) feeding tube. Control group (25) received conventional treatment only. Temperature was measured every 2 hours. The antipyretic measures used were the same across all patients enrolled. The primary outcome was number of patients diagnosed with central hyperthermia. After the discharge of all patients, there was a statistically significant difference between the 2 groups in number of patients diagnosed with central hyperthermia (6 (24%) in bromocriptine group Vs 18 (72%) in control, p = 0.002). There were no differences in hospital length of stay (p = 0.904) or mortality (p = 0.393). Early administration of bromocriptine in severe TBI may be associated with lower incidence of central hyperthermia with no effect on length of stay or mortality.展开更多
Introduction: Poly cystic ovary (PCO) is one of the most common endocrine disorders in women. All patients with PCO are at risk of insulin resistance, IFG and diabetes. Recently, bromocriptine is used in treatment of ...Introduction: Poly cystic ovary (PCO) is one of the most common endocrine disorders in women. All patients with PCO are at risk of insulin resistance, IFG and diabetes. Recently, bromocriptine is used in treatment of diabetes mellitus type II to improve insulin resistance. Objective: The aim of this study is the evaluation of bromocriptine on insulin resistance in PCO people. Patients and Methods: In this single-blind controlled clinical trial with placebo, 44 patients with PCO referring to endocrinology clinic were evaluated. Inclusion criteria were BMI > 25 kg/m2 and diagnosed PCO patients according to Rotterdam criteria and rule out other causes. Blood samples were obtained for FBS, Fasting Insulin, Prolactin, TSH and 17(OH)P. They divided two groups: Case group was given bromocriptine 2.5 mg daily and placebo was given to control group. Patients were treated for 8 days and in day 9th blood sample was obtained for FBS, Fasting insulin, HOMA-IR index. Mann-Whitney method is used for mean comparison. Results: Data analysis using showed in pre diabetes range, mean changes of FBS, insulin level and IR in Groups 1 and 2 had significant differences(P = 0.004), but no significant different was found in FBS < 100 mg/dl (P = 0.92). In group with BMI 2, no significant differences were found in changes in FBS < insulin level and IR (P = 0.13, 0.13, and 0.11 respectively). In group with BMI ≥ 30 kg/m2, no significant differences were found in changes in insulin level and IR (P = 0.69, 0.089 respectively). Mean systolic blood pressure changes in Group 1 and 2 in FBS > 100 mg/dl with (P = 0.036) were significant, but no significant difference showed in mean change of diastolic blood pressure in FBS > 100 mg/dl (P = 0.99). In FBS < 100 mg/dl mean changes in systolic and diastolic blood pressures were not significant (P = 0.6). Age showed no difference changes in effect on treatment in Groups 1 and 2 (P = 0.1). Conclusion: Our study showed, even in the short-term consumption, bromocriptine reduced FBS and insulin levels and insulin resistance in PCO patients with pre-diabetes range.展开更多
Background:To investigate the therapeutic effects of bromocriptine(BCT)combined with clomiphene citrate(CC)in the induction of ovulation in polycystic ovary syndrome(PCOS)patients with infertility.Methods:A prospectiv...Background:To investigate the therapeutic effects of bromocriptine(BCT)combined with clomiphene citrate(CC)in the induction of ovulation in polycystic ovary syndrome(PCOS)patients with infertility.Methods:A prospective,randomized,and controlled clinical trial was performed on 100 PCOS patients with infertility.Patients were randomly divided into two groups(n=50),patients in control group were treated with 50 mg CC from day 3 to day 7 of the menstrual cycle,and those in observation group(CC+BCT)were given 50 mg of CC from day 3 to day 7 of the menstrual cycle along with 2.5 mg of BCT daily for the full cycle.Patients in both groups were treated for one cycle.Blood was extracted from patients on day 3 of the menstrual cycle,the day of human chorionic gonadotrophin(hCG)injection,and day 7 after hCG injection to measure serum levels of follicle-stimulating hormone(FSH),luteinizing hormone(LH),prolactin(PRL),estradiol(E_(2)),total testosterone(T)and progestin(P).Vaginal ultrasound was used to determine the thickness of endometrium and follicle size and count.Results:There was no significant difference in basal hormone levels between two groups.The success rate of ovulation induction in control group and observation group was 72.0%and 75.4%,respectively,no significant difference was found between two groups(P>0.05).The ongoing pregnancy rate(18.4%)in observation group was significantly higher than that in control group(8.0%).On the day of hCG injection,no significant differences in the levels of FSH,E_(2),and P were found between two groups,while LH was lower,and levels of PRL and T were significantly lower in observation group than those in control group(all P=0.00).On day 7 after hCG injection,no significant differences in the levels of E_(2) and P were found between two groups,while PRL level was significantly lower in observation group than that in control group,and the endometrial thickness in observation group(10.20±1.92 mm)was significantly higher than that in control group(9.22±1.88 mm)(P=0.01).Conclusions:Compared with the use of CC alone,BCT combined with CC can increase the success rate of ovulation induction-assisted pregnancy in PCOS patients,decrease the levels of PRL,LH,and T and increase the endometrial thickness in implantation window.Those data suggest that dopamine agonist BCT may reduce the pituitary hormone and androgen levels,reduce endometrial vascular resistance,and increase endometrial blood supply to improve the infertility outcomes of PCOS patients with infertility.展开更多
17β-estradiol modulates the activity of D2 receptors in the regulation of food intake and body weight. The functional lack of 17β-estradiol in postmenopausal women could create a dietary imbalance and cause body wei...17β-estradiol modulates the activity of D2 receptors in the regulation of food intake and body weight. The functional lack of 17β-estradiol in postmenopausal women could create a dietary imbalance and cause body weight gain. This study aimed to better understand the interferences that could exist between 17β-estradiol, D2 receptors and the selection of carbohydrate, fat and protein consumption, as well as their consequences on body weight gain by using an animal model of the menopause. Ovariectomy exacerbates the consumption of foods rich in lipids. Thus confirming an inhibitory action of 17β-estradiol (E2) on the consumption of these types of foods. This consumption stimulates body weight gain, which is promoted by the high caloric content of these foods and not by the amount consumed. Our results showed a direct involvement of D2 receptors in food choice. This choice would be made according to the two (2) isoforms of the D2 receptors. The D2/BR isoform directs towards a high carbohydrate consumption, without causing a gain in body weight. While D2/SUL, promotes high fat food consumption, causing an increase in body weight. In women, 17β-estradiol modulates the activity ratio between these two D2 receptor isoforms to ensure energy and homeostatic balance, stabilizing food intake and body weight.展开更多
Background: Mechanisms underlying overeating-induced obesity in post-menopausal woman include functional lack of 17β-estradiol dysregulating dopamine D2 receptors, thereby inducing food addiction, glucose craving or ...Background: Mechanisms underlying overeating-induced obesity in post-menopausal woman include functional lack of 17β-estradiol dysregulating dopamine D2 receptors, thereby inducing food addiction, glucose craving or alcohol dependence through reward circuitry. This study aimed at further understanding 17β-estradiol and dopamine D2 receptors interferences in the etiology of woman obesity. Method: Seventy-two Wistar female rats weighing 200 - 205 g, individually-housed, were divided into non-ovariectomized control (C = 6 groups) and ovariectomized rats (OVX = 6 groups) which were concurrently subjected to the following treatments: Non-drug-treated (DMSO vehicle), 17β-estradiol (E2, 5 μg/kg, s.c.), sulpiride (SUL, 20 mg/kg, i.p.), bromocriptine (BR, 0.1 mg/kg, i.p.), E2 + SUL or E2 + BR, designating the 6 constitutive groups of either control or ovariectomy. Within each experimental group, consumption of different solutions (10% alcohol, 10% sucrose and water) as well as food intake and body weight were daily measured, for 10 consecutive days. Results: This study indicated that D2S was a specific inducer of alcohol and food intakes, but reduced sugar consumption. In addition, 17β- estradiol regulated the body weight set point, modulating D2S functions towards increased food intake at lower weights and decreased food intake at higher weights. D2S met the slow genomic actions induced by 17β-estradiol. Conversely, D2L inhibited alcohol and food intakes, but induced specifically sugar consumption, thereby regulating blood glucose levels and promoting energy expenditure in reducing body weight. Indeed, 17β-estradiol exerted a tonic inhibition on D2L which was released by OVX, exacerbating sugar intake and increasing body weight. D2L mediated the rapid metabolic effects of 17β-estradiol. Conclusion: Our results supported physiological data reporting that activation of the mostly expressed presynaptically D2S-class autoreceptors decreased dopamine release stimulating food intake, whereas activation of the predominantly postsynaptic isoform D2L receptors increased dopamine activity inhibiting food intake. Our studies indicated that 17β-estradiol acted on the two types of D2 receptors showing opposite functions to equilibrate energy intake vs. expenditure for weight set point regulation. Our data also supported biochemical findings reporting that 17β-estradiol induced D2 genes transcriptional regulation, thereby involving both types of D2 receptors in the etiology of obesity. The combined dysregulated effects of D2L and D2S receptors, as 17β-estradiol was lacking, would be causal factors underlying the etiology of obesity.展开更多
Objective: Hypothyroidism has been claimed to generate sexual dysfunctions such as ejaculatory disorders. Aframomum melegueta is an aphrodisiac plant with pro-ejaculatory properties. We investigated the protective eff...Objective: Hypothyroidism has been claimed to generate sexual dysfunctions such as ejaculatory disorders. Aframomum melegueta is an aphrodisiac plant with pro-ejaculatory properties. We investigated the protective effects of aqueous extract(AE) and methanolic extract(ME) of A. melegueta on the ejaculatory function of hypothyroid male rats.Methods: Forty sexually experienced male rats were partitioned into 8 groups(5 rats per group) and treated for 28 d as follows: Group 1, Control;Group 2, propylthiouracil(PTU, 10 mg/kg)+ distilled water(DW,10 m L/kg);Group 3, PTU + 5% Tween 80(10 m L/kg);Group 4, PTU + bromocriptine(6 mg/kg);Group 5,PTU + AE(20 mg/kg);Group 6, PTU + AE(100 mg/kg);Group 7, PTU + ME(20 mg/kg), and Group 8,PTU + ME(100 mg/kg). On days 0, 7, 14 and 28 of treatment, each male rat was paired with primed receptive female for measurement of ejaculatory latency time(ELT) and post-ejaculatory interval(PEI) for1.5 h. On day 29, each male rat was urethane-anesthetized and the spinal cord was transected.Thereafter, following urethral/penile stimulations and intravenous injection of dopamine, contractions of the bulbospongiosus muscles and the intraseminal pressure were registered. After these recordings,blood was collected through the catheterization of abdominal artery and plasma was used for thyroidstimulating hormone(TSH), prolactin and testosterone assays.Results: PTU-induced hypothyroidism was characterized by a significant elevation(P < 0.001) of plasmatic TSH and prolactin levels, but a decline(P < 0.001) in plasmatic testosterone, compared to untreated group. ELT, PEI, contractions of the bulbospongiosus muscles and the intraseminal pressure were also altered by PTU treatment. On the contrary, A. melegueta extracts elevated testosterone(AE, 100 mg/kg,P < 0.01;ME, 100 mg/kg, P < 0.05) and decreased prolactin(AE, 100 mg/kg, P < 0.05;ME, 20 mg/kg,P < 0.05) levels, compared to corresponding controls. With regard to DW + PTU group, prolactin concentration was lowered(P < 0.05) in rats administered with bromocriptine. Treatment with A. melegueta extracts significantly prevented the lengthening of ELT(P < 0.05) and PEI(P < 0.001). Hypothyroid state also altered the fictive ejaculation by increasing the latency and decreasing the number and frequency of bulbospongiosus muscle contractions. There was also a decrease in the intraseminal pressure. These alterations were significantly(P < 0.05) alleviated in plant extract-treated groups.Conclusion: This study highlighted the ejaculatory disturbance of hypothyroidism in male rats and its prevention with A. melegueta extracts.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82071376(to ZC)and 82001471(to CJ)the Natural Science Foundation of Shanghai,No.20ZR1410500(to ZC).
文摘Recent studies have revealed that lipid droplets accumulate in neurons after brain injury and evoke lipotoxicity,damaging the neurons.However,how lipids are metabolized by spinal cord neurons after spinal cord injury remains unclear.Herein,we investigated lipid metabolism by spinal cord neurons after spinal cord injury and identified lipid-lowering compounds to treat spinal cord injury.We found that lipid droplets accumulated in perilesional spinal cord neurons after spinal cord injury in mice.Lipid droplet accumulation could be induced by myelin debris in HT22 cells.Myelin debris degradation by phospholipase led to massive free fatty acid production,which increased lipid droplet synthesis,β-oxidation,and oxidative phosphorylation.Excessive oxidative phosphorylation increased reactive oxygen species generation,which led to increased lipid peroxidation and HT22 cell apoptosis.Bromocriptine was identified as a lipid-lowering compound that inhibited phosphorylation of cytosolic phospholipase A2 by reducing the phosphorylation of extracellular signal-regulated kinases 1/2 in the mitogen-activated protein kinase pathway,thereby inhibiting myelin debris degradation by cytosolic phospholipase A2 and alleviating lipid droplet accumulation in myelin debris-treated HT22 cells.Motor function,lipid droplet accumulation in spinal cord neurons and neuronal survival were all improved in bromocriptine-treated mice after spinal cord injury.The results suggest that bromocriptine can protect neurons from lipotoxic damage after spinal cord injury via the extracellular signal-regulated kinases 1/2-cytosolic phospholipase A2 pathway.
文摘Dopamine agonists effectively reduce the secretion of prolactin (PRL) in the great majority of prolactinomas and reduce the bulk of the adenomas, as well as have partial therapeutic effect on some patients with acromegaly. The inhibitory effect of bromocriptine (BC), a dopamine agonist, on growth hormone (GH) and PRL secretion of dispersed cells from the pituitary adenomas of 16 cases of acromegaly, which secret GH and PRL simultaneously, were evaluated in vitro. The significant inhibitory effects of BC on PRL secretion were found in 12 cases. It was also found that PRL secretion was strongly inhibited when GH was suppressed; on the contrary, when GH secretion was not suppressed, the production of PRL was not or weakly inhibited. The exact mechanism of the effects is nuclear so far. It is necessary to investigate, at molecular level, the etiology of GH-PRL adenomas and its response to therapeutic agents.
文摘BACKGROUND Some patients present to the intensive care unit due to noninfectious pathologies resulting in fever,especially acute neurological injuries,including brain trauma and intracranial haemorrhage.The cause has been identified to be central hyperthermia characterized by a high core temperature and a poor response to antipyretics and antibiotics.However,no proper guidelines on how to treat central hyperthermia have been developed for clinical practice.CASE SUMMARY A 63-year-old woman was transferred to our hospital due to injury after a traffic accident.Eight hours after admission,her pupils enlarged bilaterally from 2.5 mm to 4.0 mm.She developed severe coma and underwent decompressive craniectomy.She was diagnosed with central hyperthermia after surgery and was prescribed bromocriptine.The standard dose of bromocriptine could not control her hyperpyrexia,and we prescribed 30 mg a day to control her temperature.CONCLUSION Bromocriptine may be effective in controlling central hyperthermia and have a dosage effect.
文摘Strong evidence showed that fever after traumatic brain injury TBI is associated with increased mortality. In this study, we tried to evaluate the role of Bromocriptine in central hyperthermia in patients with severe TBI. This prospective controlled study was conducted on 50 severe TBI patients who admitted to the critical care department and confirmed on Computed Tomography (CT) of the brain and GCS of less than 9 at admission. Then, they were randomly assigned into 2 groups. Bromocriptine group (25) received bromocriptine 7.5 mg/day during 24 hours from admission through a naso-gastric (NG) feeding tube. Control group (25) received conventional treatment only. Temperature was measured every 2 hours. The antipyretic measures used were the same across all patients enrolled. The primary outcome was number of patients diagnosed with central hyperthermia. After the discharge of all patients, there was a statistically significant difference between the 2 groups in number of patients diagnosed with central hyperthermia (6 (24%) in bromocriptine group Vs 18 (72%) in control, p = 0.002). There were no differences in hospital length of stay (p = 0.904) or mortality (p = 0.393). Early administration of bromocriptine in severe TBI may be associated with lower incidence of central hyperthermia with no effect on length of stay or mortality.
文摘Introduction: Poly cystic ovary (PCO) is one of the most common endocrine disorders in women. All patients with PCO are at risk of insulin resistance, IFG and diabetes. Recently, bromocriptine is used in treatment of diabetes mellitus type II to improve insulin resistance. Objective: The aim of this study is the evaluation of bromocriptine on insulin resistance in PCO people. Patients and Methods: In this single-blind controlled clinical trial with placebo, 44 patients with PCO referring to endocrinology clinic were evaluated. Inclusion criteria were BMI > 25 kg/m2 and diagnosed PCO patients according to Rotterdam criteria and rule out other causes. Blood samples were obtained for FBS, Fasting Insulin, Prolactin, TSH and 17(OH)P. They divided two groups: Case group was given bromocriptine 2.5 mg daily and placebo was given to control group. Patients were treated for 8 days and in day 9th blood sample was obtained for FBS, Fasting insulin, HOMA-IR index. Mann-Whitney method is used for mean comparison. Results: Data analysis using showed in pre diabetes range, mean changes of FBS, insulin level and IR in Groups 1 and 2 had significant differences(P = 0.004), but no significant different was found in FBS < 100 mg/dl (P = 0.92). In group with BMI 2, no significant differences were found in changes in FBS < insulin level and IR (P = 0.13, 0.13, and 0.11 respectively). In group with BMI ≥ 30 kg/m2, no significant differences were found in changes in insulin level and IR (P = 0.69, 0.089 respectively). Mean systolic blood pressure changes in Group 1 and 2 in FBS > 100 mg/dl with (P = 0.036) were significant, but no significant difference showed in mean change of diastolic blood pressure in FBS > 100 mg/dl (P = 0.99). In FBS < 100 mg/dl mean changes in systolic and diastolic blood pressures were not significant (P = 0.6). Age showed no difference changes in effect on treatment in Groups 1 and 2 (P = 0.1). Conclusion: Our study showed, even in the short-term consumption, bromocriptine reduced FBS and insulin levels and insulin resistance in PCO patients with pre-diabetes range.
基金This study was supported by the project of Shanghai Association for Science and Technology(KXSH021311).
文摘Background:To investigate the therapeutic effects of bromocriptine(BCT)combined with clomiphene citrate(CC)in the induction of ovulation in polycystic ovary syndrome(PCOS)patients with infertility.Methods:A prospective,randomized,and controlled clinical trial was performed on 100 PCOS patients with infertility.Patients were randomly divided into two groups(n=50),patients in control group were treated with 50 mg CC from day 3 to day 7 of the menstrual cycle,and those in observation group(CC+BCT)were given 50 mg of CC from day 3 to day 7 of the menstrual cycle along with 2.5 mg of BCT daily for the full cycle.Patients in both groups were treated for one cycle.Blood was extracted from patients on day 3 of the menstrual cycle,the day of human chorionic gonadotrophin(hCG)injection,and day 7 after hCG injection to measure serum levels of follicle-stimulating hormone(FSH),luteinizing hormone(LH),prolactin(PRL),estradiol(E_(2)),total testosterone(T)and progestin(P).Vaginal ultrasound was used to determine the thickness of endometrium and follicle size and count.Results:There was no significant difference in basal hormone levels between two groups.The success rate of ovulation induction in control group and observation group was 72.0%and 75.4%,respectively,no significant difference was found between two groups(P>0.05).The ongoing pregnancy rate(18.4%)in observation group was significantly higher than that in control group(8.0%).On the day of hCG injection,no significant differences in the levels of FSH,E_(2),and P were found between two groups,while LH was lower,and levels of PRL and T were significantly lower in observation group than those in control group(all P=0.00).On day 7 after hCG injection,no significant differences in the levels of E_(2) and P were found between two groups,while PRL level was significantly lower in observation group than that in control group,and the endometrial thickness in observation group(10.20±1.92 mm)was significantly higher than that in control group(9.22±1.88 mm)(P=0.01).Conclusions:Compared with the use of CC alone,BCT combined with CC can increase the success rate of ovulation induction-assisted pregnancy in PCOS patients,decrease the levels of PRL,LH,and T and increase the endometrial thickness in implantation window.Those data suggest that dopamine agonist BCT may reduce the pituitary hormone and androgen levels,reduce endometrial vascular resistance,and increase endometrial blood supply to improve the infertility outcomes of PCOS patients with infertility.
文摘17β-estradiol modulates the activity of D2 receptors in the regulation of food intake and body weight. The functional lack of 17β-estradiol in postmenopausal women could create a dietary imbalance and cause body weight gain. This study aimed to better understand the interferences that could exist between 17β-estradiol, D2 receptors and the selection of carbohydrate, fat and protein consumption, as well as their consequences on body weight gain by using an animal model of the menopause. Ovariectomy exacerbates the consumption of foods rich in lipids. Thus confirming an inhibitory action of 17β-estradiol (E2) on the consumption of these types of foods. This consumption stimulates body weight gain, which is promoted by the high caloric content of these foods and not by the amount consumed. Our results showed a direct involvement of D2 receptors in food choice. This choice would be made according to the two (2) isoforms of the D2 receptors. The D2/BR isoform directs towards a high carbohydrate consumption, without causing a gain in body weight. While D2/SUL, promotes high fat food consumption, causing an increase in body weight. In women, 17β-estradiol modulates the activity ratio between these two D2 receptor isoforms to ensure energy and homeostatic balance, stabilizing food intake and body weight.
文摘Background: Mechanisms underlying overeating-induced obesity in post-menopausal woman include functional lack of 17β-estradiol dysregulating dopamine D2 receptors, thereby inducing food addiction, glucose craving or alcohol dependence through reward circuitry. This study aimed at further understanding 17β-estradiol and dopamine D2 receptors interferences in the etiology of woman obesity. Method: Seventy-two Wistar female rats weighing 200 - 205 g, individually-housed, were divided into non-ovariectomized control (C = 6 groups) and ovariectomized rats (OVX = 6 groups) which were concurrently subjected to the following treatments: Non-drug-treated (DMSO vehicle), 17β-estradiol (E2, 5 μg/kg, s.c.), sulpiride (SUL, 20 mg/kg, i.p.), bromocriptine (BR, 0.1 mg/kg, i.p.), E2 + SUL or E2 + BR, designating the 6 constitutive groups of either control or ovariectomy. Within each experimental group, consumption of different solutions (10% alcohol, 10% sucrose and water) as well as food intake and body weight were daily measured, for 10 consecutive days. Results: This study indicated that D2S was a specific inducer of alcohol and food intakes, but reduced sugar consumption. In addition, 17β- estradiol regulated the body weight set point, modulating D2S functions towards increased food intake at lower weights and decreased food intake at higher weights. D2S met the slow genomic actions induced by 17β-estradiol. Conversely, D2L inhibited alcohol and food intakes, but induced specifically sugar consumption, thereby regulating blood glucose levels and promoting energy expenditure in reducing body weight. Indeed, 17β-estradiol exerted a tonic inhibition on D2L which was released by OVX, exacerbating sugar intake and increasing body weight. D2L mediated the rapid metabolic effects of 17β-estradiol. Conclusion: Our results supported physiological data reporting that activation of the mostly expressed presynaptically D2S-class autoreceptors decreased dopamine release stimulating food intake, whereas activation of the predominantly postsynaptic isoform D2L receptors increased dopamine activity inhibiting food intake. Our studies indicated that 17β-estradiol acted on the two types of D2 receptors showing opposite functions to equilibrate energy intake vs. expenditure for weight set point regulation. Our data also supported biochemical findings reporting that 17β-estradiol induced D2 genes transcriptional regulation, thereby involving both types of D2 receptors in the etiology of obesity. The combined dysregulated effects of D2L and D2S receptors, as 17β-estradiol was lacking, would be causal factors underlying the etiology of obesity.
文摘Objective: Hypothyroidism has been claimed to generate sexual dysfunctions such as ejaculatory disorders. Aframomum melegueta is an aphrodisiac plant with pro-ejaculatory properties. We investigated the protective effects of aqueous extract(AE) and methanolic extract(ME) of A. melegueta on the ejaculatory function of hypothyroid male rats.Methods: Forty sexually experienced male rats were partitioned into 8 groups(5 rats per group) and treated for 28 d as follows: Group 1, Control;Group 2, propylthiouracil(PTU, 10 mg/kg)+ distilled water(DW,10 m L/kg);Group 3, PTU + 5% Tween 80(10 m L/kg);Group 4, PTU + bromocriptine(6 mg/kg);Group 5,PTU + AE(20 mg/kg);Group 6, PTU + AE(100 mg/kg);Group 7, PTU + ME(20 mg/kg), and Group 8,PTU + ME(100 mg/kg). On days 0, 7, 14 and 28 of treatment, each male rat was paired with primed receptive female for measurement of ejaculatory latency time(ELT) and post-ejaculatory interval(PEI) for1.5 h. On day 29, each male rat was urethane-anesthetized and the spinal cord was transected.Thereafter, following urethral/penile stimulations and intravenous injection of dopamine, contractions of the bulbospongiosus muscles and the intraseminal pressure were registered. After these recordings,blood was collected through the catheterization of abdominal artery and plasma was used for thyroidstimulating hormone(TSH), prolactin and testosterone assays.Results: PTU-induced hypothyroidism was characterized by a significant elevation(P < 0.001) of plasmatic TSH and prolactin levels, but a decline(P < 0.001) in plasmatic testosterone, compared to untreated group. ELT, PEI, contractions of the bulbospongiosus muscles and the intraseminal pressure were also altered by PTU treatment. On the contrary, A. melegueta extracts elevated testosterone(AE, 100 mg/kg,P < 0.01;ME, 100 mg/kg, P < 0.05) and decreased prolactin(AE, 100 mg/kg, P < 0.05;ME, 20 mg/kg,P < 0.05) levels, compared to corresponding controls. With regard to DW + PTU group, prolactin concentration was lowered(P < 0.05) in rats administered with bromocriptine. Treatment with A. melegueta extracts significantly prevented the lengthening of ELT(P < 0.05) and PEI(P < 0.001). Hypothyroid state also altered the fictive ejaculation by increasing the latency and decreasing the number and frequency of bulbospongiosus muscle contractions. There was also a decrease in the intraseminal pressure. These alterations were significantly(P < 0.05) alleviated in plant extract-treated groups.Conclusion: This study highlighted the ejaculatory disturbance of hypothyroidism in male rats and its prevention with A. melegueta extracts.
