Single nucleotide polymorphisms （SNP） of chicken gonadotropin-releasing hormone receptor （GnRHR） and neuropeptide Y （NPY） were selected to identify the genotypes of Wenchang （Chinese indigenous breed） chicken ...Single nucleotide polymorphisms （SNP） of chicken gonadotropin-releasing hormone receptor （GnRHR） and neuropeptide Y （NPY） were selected to identify the genotypes of Wenchang （Chinese indigenous breed） chicken with restricton fragment length polymorphisms. The associations of the SNPs with the total egg production （NE）, average days of continual laying （ADCL）, and number of double-yolked eggs （DYE） traits were analyzed. The frequency of restriction enzyme A/a alleles in the population was for GnRHR 0.69 （Bpu1102 Ⅰ A） and 0.31 （Bpu1102 Ⅰ a） and for NPY 0.46 （Dra Ⅰ B） and 0.54 （Dra Ⅰ b）. Trait data from a total of 120 hens, which were purebred introduced from Hainan Province, China from one generation were recorded. Two significant effects of genes＇ marker were found： for GnRHR and number of eggs （dominant; t= 2.67, df= 116） and NPY and number of eggs （additive; t= 1.97, df= 116）. The current research supports the effects of GnRHR and NPY genes on egg-laying traits of chickens.展开更多
The clinical outcomes of five groups of infertility patients receiving frozen- thawed, cleavage-stage embryo transfers with exogenous hormone protocols with or without a depot gonadotropin-releasing hormone （GnRH） a...The clinical outcomes of five groups of infertility patients receiving frozen- thawed, cleavage-stage embryo transfers with exogenous hormone protocols with or without a depot gonadotropin-releasing hormone （GnRH） agonist were assessed. A retrospective cohort analysis was performed on 1003 cycles undergoing frozen-thawed, cleavage-stage embryo transfers from January 1, 2012 to June 31, 2015 in the Reproductive Medicine Center of Wuhan General Hospital of Guangzhou Military Region. Based on the infertility etiologies of the patients, the 1003 cycles were divided into five groups： tubal infertility, polycystic ovary syndrome （PCOS）, endometriosis, male infertility, and unexplained infertility. The main outcome was the live birth rate. Two groups were set up based on the intervention： group A was given a GnRH agonist with exogenous estrogen and progesterone, and group B （control group） was given exogenous estrogen and progesterone only. The results showed that the baseline serum hormone levels and basic characteristics of the patients were not significantly different between groups A and B. The live birth rates in groups A and B were 41.67% and 29.29%, respectively （P〈0.05）. The live birth rates in patients with PCOS in groups A and B were 56.25% and 30.61%, respectively （P〈0.05）. The clinical pregnancy, implantation and on-going pregnancy rates showed the same trends as the live birth rates between groups A and B. The ectopic pregnancy rate was significantly lower in group A than in group B. We concluded that the live birth rate was higher and other clinical outcomes were more satisfactory with GnRH agonist co- treatment than without GnRH agonist co-treatment for frozen-thawed embryo transfer. The GnRH agonist combined with exogenous estrogen and progesterone worked for all types of infertility tested, especially for women with PCOS.展开更多
[ Objective] To locate gonadotropin-releasing hormone （GnRH） in pituitary of Guangxi swamp buffaloes and to provide a theoretical ba- sis for cloning and sequence analysis of GnRH receptor gene. [ Method] GnRH in pi...[ Objective] To locate gonadotropin-releasing hormone （GnRH） in pituitary of Guangxi swamp buffaloes and to provide a theoretical ba- sis for cloning and sequence analysis of GnRH receptor gene. [ Method] GnRH in pituitary were immunohistochemically stained by avidin biotin complex method. The GnRH expression was analyzed with image system. The GnRH receptor gene was amplified by real-time PCR. [ Result] Many GnRH positive cells were detected in pars distalis of adenohypophysis. GnRH were distributed in cytoplasm but not in nuclei. No positive sig- nal was observed in neurohypophysis. In addition, the GnRH receptor gene, 920 bp in size, was amplified. [ Conclusion] A large number of GnRH and GnRH receptor were found in pars distalis of adenohypophysis, which indicates that anterior pituitary is an important tissue for functions of hypo- thalamus-pituitary-gonadal axis and other endocrine axes.展开更多
The hypothalamic Arg-Phe-amide-related peptides, gonadotropin-inhibitory hormone and orthologous mammalian peptides of Arg-Phe-amide, may be important regulators of the hypothalamus-pituitary-gonadal reproductive axis...The hypothalamic Arg-Phe-amide-related peptides, gonadotropin-inhibitory hormone and orthologous mammalian peptides of Arg-Phe-amide, may be important regulators of the hypothalamus-pituitary-gonadal reproductive axis. These peptides may modulate the effects of kisspeptins because they are presently recognized as the most potent activators of the hypothalamus-pituitary-gonadal axis. However, their effects on gonadotropin-releasing hormone neurons have not been investigated. In the current study, the GT1-7 cell line-expressing gonadotropin-releasing hormone was used as a model to explore the effects of Arg-Phe- amide-related peptides on kisspeptin activation. Intracellular calcium concentration was quantified using the calcium-sensitive dye, fura-2 acetoxymethyl ester. Gonadotropin-releasing hormone released into the medium was detected via enzyme-linked immunosorbent assay. Results showed that 100 nmol/L kisspeptin-10 significantly increased gonadotropin-releasing hormone levels （at 120 minutes of exposure） and intracellular calcium concentrations. Co-treatment of kisspeptin with 1 μmol/L gonadotropin-inhibitory hormone or 1 μmol/L Arg-Phe-amide-related peptide-1 significantly attenuated levels of kisspeptin-induced gonadotropin-releasing hormone but did not affect kisspeptin-induced elevations of intracellular calcium concentration. Overall, the results suggest that gonadotropin-inhibitory hormone and Arg-Phe-amide-related peptide-1 may have inhibitory effects on kisspeptin-activated gonadotropin-releasing hormone neurons independent of the calcium signaling pathway.展开更多
Gonadotropin-releasing hormone （GnRH） neurons in the preoptic area may undergo morphological changes during the pubertal period when their activities are upregulated. To clarify the regulatory mechanism of puberty o...Gonadotropin-releasing hormone （GnRH） neurons in the preoptic area may undergo morphological changes during the pubertal period when their activities are upregulated. To clarify the regulatory mechanism of puberty onset, this study aimed to investigate the morphological changes of GnRH neurons in the preoptic area of GnRH-enhanced green fluorescent protein transgenic rats. Under confocal laser microscopy, pubertal GnRH neurons exhibited an inverted Y distribution pattern. Prepubertal GnRH neurons were generally unipolar and bipolar, and were distinguished as smooth type cells with few small processes or irregular type cells with many spine-like processes in the proximal dendrites. The number of GnRH neurons in the preoptic area and spine-like processes were increased during the course of reproductive maturation. There was no significant difference between male and female rats. Immunofluorescence staining revealed synaptophysin punctae close to the distal end of GnRH neurons, indicating that some presynaptic terminals may form a synaptic linkage with these neurons.展开更多
Kisspeptin is essential for activation of the hypothalamo-pituitary-gonadal axis. In this study, we established gonadotropin-releasing hormone/enhanced green fluorescent protein transgenic rats. Rats were injected wit...Kisspeptin is essential for activation of the hypothalamo-pituitary-gonadal axis. In this study, we established gonadotropin-releasing hormone/enhanced green fluorescent protein transgenic rats. Rats were injected with 1, 10, or 100 pM kisspeptin-10, a peptide derived from full-length kisspeptin, into the arcuate nucleus and medial preoptic area, and with the kJsspeptJn antagonist peptJde 234 into the lateral cerebral ventricle. The results of immunohistochemical staining revealed that pulsatile luteinizing hormone secretion was suppressed after injection of antagonist peptide 234 into the lateral cerebral ventricle, and a significant increase in luteinizing hormone level was observed after kisspeptin-10 injection into the arcuate nucleus and medial preoptic area. The results of an enzyme-linked immunosorbent assay showed that luteinizing hormone levels during the first hour of kisspeptin-10 infusion into the arcuate nucleus were significantly greater in the 100 pM kisspeptin-10 group than in the 10 pM kisspeptin-10 group. These findings indicate that kisspeptin directly promotes gonadotropin-releasing hormone secretion and luteinizing hormone release in gonadotropin-releasing hormone/enhanced green fluorescent protein transgenic rats. The arcuate nucleus is a key component of the kisspeptin-G protein-coupled receptor 54 signaling pathway underlying regulating luteinizing hormone pulse secretion.展开更多
Objective It is well known that a dual trigger treatment can improve clinical outcomes of in vitro fertilization(IVF)in high or normal ovarian responders.However,it is not clear whether dual triggering also benefits p...Objective It is well known that a dual trigger treatment can improve clinical outcomes of in vitro fertilization(IVF)in high or normal ovarian responders.However,it is not clear whether dual triggering also benefits patients with diminished ovarian reserve(DOR).The aim of this study was to investigate whether a dual trigger treatment of gonadotropin-releasing hormone(GnRH)agonist combined with human chorionic gonadotropin(hCG)for final follicular maturation improves the cumulative live birth rate(CLBR)during the GnRH-antagonist cycle in patients with DOR.Methods This retrospective study included patients with DOR who received a GnRH-antagonist protocol during IVF and intracytoplasmic sperm injection(IVF-ICSI)cycles at Peking University People’s Hospital from January 1,2017 through December 31,2017.Oocyte maturation was triggered by GnRH combined with hCG(n=110)or hCG alone(n=71).Embryos were transferred on the third day after oocyte retrieval or during a subsequent freeze-thaw cycle.Patients were followed up for 3 years.Results The dual trigger treatment did not affect CLBR,which is an overall determinant of the success rate of assisted reproductive technology(ART).Women in the dual trigger group had significantly higher rates of fertilization than those in the hCG group(90.1%vs.83.9%,P=0.040).Conclusion Dual trigger with GnRH agonist and hCG did not improve CLBR in patients with DOR,but did slightly improve fertilization rate,oocyte count,and embryo quality.展开更多
目的比较卵巢子宫内膜异位囊肿(OEC)剔除术后辅以地诺孕素与促性腺激素释放激素激动剂(GnRH-a)治疗后患者疼痛和疾病复发率的差异。方法本研究为随机对照试验。依据随机硬币投掷法,将2020年5月至2022年4月西电集团医院妇产科符合OEC剔...目的比较卵巢子宫内膜异位囊肿(OEC)剔除术后辅以地诺孕素与促性腺激素释放激素激动剂(GnRH-a)治疗后患者疼痛和疾病复发率的差异。方法本研究为随机对照试验。依据随机硬币投掷法,将2020年5月至2022年4月西电集团医院妇产科符合OEC剔除术治疗标准的113例患者分为GnRH-a组(61例)和地诺组(52例)。GnRH-a组年龄(35.38±4.49)岁;病程(3.28±1.04)年;囊肿大小6.00(5.00,8.00)cm;美国生殖医学学会(American Society for Reproductive Medicine,ASRM)分期:Ⅰ~Ⅱ期30例,Ⅲ~Ⅳ期31例。地诺组年龄(35.52±4.61)岁;病程(3.52±1.06)年;囊肿大小6.00(5.00,8.00)cm;ASRM分期:Ⅰ~Ⅱ期26例,Ⅲ~Ⅳ期26例。从剔除术后首次月经来潮的第1天开始,GnRH-a组采用腹前壁皮下注射醋酸亮丙瑞林进行辅助治疗,3.75 mg/次,4周一次;地诺组口服地诺孕素片进行辅助治疗,2 mg/次,每天一次。两组均持续治疗24周。比较两组视觉模拟评分法(VAS)评分、不良反应、复发率和治疗满意度。采用独立样本t检验、非参数Wilcoxon检验、Mann-Whitney U检验、χ2检验进行统计学分析。结果用药24周后,地诺组痛经、慢性盆腔痛和性交痛VAS评分均低于GnRH-a组[0.50(0,2.00)分比1.00(0,3.00)分,1.00(0,3.00)分比2.00(1.00,4.00)分,0(0,2.00)分比1.00(0,2.00)分](Z=2.396、2.669、2.929,均P<0.05)。GnRH-a组和地诺组不良反应发生率和停药后12个月复发率比较[14.75%(9/61)比5.77%(3/52),8.20%(5/61)比1.92%(1/52)],差异均无统计学意义(χ2=2.378、2.197,均P>0.05)。地诺组治疗总满意度高于GnRH-a组[94.23%(49/52)比81.97%(50/61)](χ2=3.889,P<0.05)。结论相较于GnRH-a,OEC剔除术后辅以地诺孕素能有效缓解患者疼痛,预防疾病复发,获得更高的治疗满意度。展开更多
Background： Luteal support is a key to patients undergoing in vitro fertilization and embryo transfer （IVF-ET） with gonadotropin-releasing hormone （GnRH）-antagonist protocol. This study aimed to compare the effec...Background： Luteal support is a key to patients undergoing in vitro fertilization and embryo transfer （IVF-ET） with gonadotropin-releasing hormone （GnRH）-antagonist protocol. This study aimed to compare the effect between vaginal progesterone （VP） and intramuscular progesterone （IMP） with GnRH-antagonist protocol alter IVF-ET. Methods： A total of 1760 patients （18 years ≤ age ≤35 years） undergoing IVF-ET with GnRH-antagonist protocol were studied retrospectively between September 2014 and August 2015 in Peking University Third Hospital. In the patients, 1341 patients received VP （VP group） and 419 patients received IMP （IMP group） as luteal support. We compared clinical outcomes between these two groups. The primary objective of the study was the live birth rate. Measurement data between the two groups were conducted using independent samples t-test. The variables in line with non-normal distribution were expressed as median （p25 and p75） and were compared using nonparametric Mann. Whitney U-test. Results： Live birth rate in VP group was 38.55%, significantly higher than that in the IMP group, which was 30.79% （x^2 = 8.287, P= 0.004）. The clinical intrauterine pregnancy rate and implantation rate in VP group were also significantly higher than those in the IMP group （clinical intrauterine pregnancy rate 47.35% vs. 41.29%, x^2= 4.727, P = 0.030： implantation rate 30.99% vs. 25.26%, x^2=14.546, P 〈 0.001）. Any statistically significant differences in ectopic pregnancy and abortion rates between two groups were not observed. Conclusion： Luteal support with VP had better clinical outcomes for young women undergoing IVF-ET with GnRH-antagonist protocol.展开更多
Background Type I gonadotropin-releasing hormone （GnRH-l） agonists have been applied for the treatment of steroid-dependent tumors such as breast carcinoma, ovarian cancer and prostatic carcinoma. But the mechanism ...Background Type I gonadotropin-releasing hormone （GnRH-l） agonists have been applied for the treatment of steroid-dependent tumors such as breast carcinoma, ovarian cancer and prostatic carcinoma. But the mechanism has not been clarified yet. There are few reports about the treatment of endometrial carcinoma using GnRH-l agonists. Type II GnRH （GnRH-ll） is a new subtype of GnRH. Our aim was to investigate the effects of GnRH-l agonists and GnRH-ll on estrogen receptor-negative human endometrial carcinoma cells and the effect from phosphatase and tensin homolog gene （PTEN） to them.Methods A lentiviral vector-mediated RNAi method was used to establish a PTEN-negative HEC-1A cell clone （HEC-1A-ND）. MTT and flow cytometry were used to detect the cell proliferation, cell cycle and apoptosis of HEC-1A, HEC-1A-NC and HEC-1A-ND cells after treatment with GnRH-l agonist Triptorelin （10-11 mol/L to 10-5 mol/L） or GnRH-ll （10-11 mol/L to 10-5 mol/L）. Western blotting was used to detect AKT and ERK1/2 activation after treatment with different concentrations of Triptorelin or GnRH-ll for 30 minutes in the above mentioned three kinds of cells. Results Triptorelin and GnRH-ll induced apoptosis and inhibited proliferation of HEC-1 A, HEC-1A-ND and HEC-1A-NC in a dose-dependent manner. This effect was augmented in HEC-1 A-ND cells in which PTEN gene was knocked-down. Furthermore, Triptorelin and GnRH-ll inhibited the AKT and ERK activity in HEC-1 A-ND cells.Conclusions Triptorelin and GnRH-ll can promote apoptosis rate and inhibit cell proliferation of estrogen receptor-negative endometrial carcinoma cells in a dose-dependent manner. PTEN gene can inhibit the effects of Triptorelin or GnRH-ll on human endometrial carcinoma cells.展开更多
Background Recently, conservative surgery is acceptable in young patients with borderline ovarian tumor and ovarian cancer. The preservation of these patients＇ future fertility has been the focus of recent interest. ...Background Recently, conservative surgery is acceptable in young patients with borderline ovarian tumor and ovarian cancer. The preservation of these patients＇ future fertility has been the focus of recent interest. This study aimed to observe the effect of gonadotropin-releasing hormone agonists （GnRHa） cotreatment during chemotherapy in borderline ovarian tumor and ovarian cancer patients. Methods Sixteen patients who were treated with fertility preservation surgery for borderline ovarian tumor and ovarian cancer and then administered GnRHa during chemotherapy in Peking University People＇s Hospital from January 2006 to July 2010 were retrospectively analyzed. This group was compared with a control group of 16 women who were treated concurrently with similar chemotherapy （n=5） without GnRHa or were historical controls （n=11）. The disease recurrence, the menstruation status and reproductive outcome were followed up and compared between the two groups. Results There were no significant differences between both groups regarding age, body weight, height, marriage status, classification of the tumors, stage of the disease, as were the cumulative doses of each chemotherapeutic agent. One （1/16） patient in the study group while 2 （2/16） patients in the control group relapsed 2 years after conclusion of the primary treatment （P 〉0.05）. All of the 16 women in the study group compared with 11 of the 16 patients in the control group resumed normal menses 6 months after the termination of the treatment （P 〈0.05）. There were 4 spontaneous pregnancies in the study group while 2 in the control group, all of the neonates were healthy. Conclusions GnRHa administration before and during chemotherapy in borderline ovarian tumor and ovarian cancer patients who had undergone fertility preservation operation may bring up higher rates of spontaneous resumption of menses and a better pregnancy rate. Long-term follow up and large scale clinical studies are required.展开更多
Background Ovarian hyperstimulation syndrome （OHSS） is one of the most life-threatening complications of assisted reproduction treatments. Gonadotropin-releasing hormone antagonists （GnRHanta） are thought to be ef...Background Ovarian hyperstimulation syndrome （OHSS） is one of the most life-threatening complications of assisted reproduction treatments. Gonadotropin-releasing hormone antagonists （GnRHanta） are thought to be effective in preventing this complication, and some clinical trials have found lower incidences of OHSS in patients treated with GnRHanta. Our aim was to investigate the effects of GnRHanta on vascular permeability and the expression of vascular endothelial growth factor （VEGF） and its receptors in a rat model of OHSS. Methods An immature early OHSS rat model was established. Three ovarian stimulation protocols were used： pregnant mare serum gonadotropin/human chorionic gonadotropin （hCG） alone, with a GnRHanta, or with a gonadotropin-releasing hormone agonists （GnRHa）. Blood and tissue samples were collected at 48 hours after hCG administration. Vascular permeability was evaluated by measuring the Evans-Blue content of extravasated peritoneal fluids. The expression of VEGF and its receptors, including fit-1 and KDR, were detected by reverse transcriptase-polymerase chain reaction and Western blotting. Results Treatment with both a GnRHanta and a GnRHa resulted in significant reductions in serum estradiol and peritoneal vascular permeability, as well as decreased ovarian expression of VEGF and its two receptors. However, GnRHanta treatment caused a greater reduction in serum estradiol concentrations, and in VEGF receptor mRNA expression than GnRHa. There were no significant reductions in the expression of VEGF or its receptors in extra-ovarian tissues, including the liver, lungs and peritoneum. Conclusion Our results reveal that GnRHanta are more potent than GnRHa in preventing early OHSS through down-regulation of the expression of VEGF and its receptors in hyperstimulated ovaries.展开更多
Background： Delayed puberty can result either from constitutional delay of growth and puberty （CDP） or idiopathic hypogonadotropic hypogonadism （IHH）. Gonadotropin-releasing hormone （GnRH） stimulation test has ...Background： Delayed puberty can result either from constitutional delay of growth and puberty （CDP） or idiopathic hypogonadotropic hypogonadism （IHH）. Gonadotropin-releasing hormone （GnRH） stimulation test has been generally accepted as a current method for diagnosing delayed puberty. The objective of this research was to assess the cut-offvalues and the efficacy of GnRH stimulation test in the diagnosis of delayed puberty in both males and females. Methods： A study of 91 IHH, 27 CDP patients, 6 prepubertal children, and 20 pubertal adults was undertaken. Blood samples were obtained at 0, 30, 60, and 120 rain after GnRH administration and the levels of luteinizing hormone （LH） and follicle-stimulating hormone （FSH） were rneast, red. For each paralneter, the sensitivities and specificities were estimated, and the receiver operating characteristic （ROC） curves were constructed. Resulis： The ROC curves indicated that a serunl basal LH 〈0.6 IU/L or peak LH 〈9.74 IU/L resulted in moderate sensitivity （73.8% or 80.0%） and specificity （90.9% or 86.4%） in the diagnosis of HH in males. Serum basal LH 〈0.85 IU/L or basal FSH 〈2.43 IU/L resulted in moderate sensitivity （80.0% or 100.0%） and specificity （75.0% or 50.0%） in the diagnosis of HH in females. Conclusions： Our data suggest that isolated use of the gonadorelin stimulation test is almost sufficient to discriminate between HH and CDP in males, but unnecessary in females. The most useful predictor is serum basal or peak LH to differentiate these two disorders in males, but serum basal LH or FSH in females.展开更多
文摘Single nucleotide polymorphisms （SNP） of chicken gonadotropin-releasing hormone receptor （GnRHR） and neuropeptide Y （NPY） were selected to identify the genotypes of Wenchang （Chinese indigenous breed） chicken with restricton fragment length polymorphisms. The associations of the SNPs with the total egg production （NE）, average days of continual laying （ADCL）, and number of double-yolked eggs （DYE） traits were analyzed. The frequency of restriction enzyme A/a alleles in the population was for GnRHR 0.69 （Bpu1102 Ⅰ A） and 0.31 （Bpu1102 Ⅰ a） and for NPY 0.46 （Dra Ⅰ B） and 0.54 （Dra Ⅰ b）. Trait data from a total of 120 hens, which were purebred introduced from Hainan Province, China from one generation were recorded. Two significant effects of genes＇ marker were found： for GnRHR and number of eggs （dominant; t= 2.67, df= 116） and NPY and number of eggs （additive; t= 1.97, df= 116）. The current research supports the effects of GnRHR and NPY genes on egg-laying traits of chickens.
文摘The clinical outcomes of five groups of infertility patients receiving frozen- thawed, cleavage-stage embryo transfers with exogenous hormone protocols with or without a depot gonadotropin-releasing hormone （GnRH） agonist were assessed. A retrospective cohort analysis was performed on 1003 cycles undergoing frozen-thawed, cleavage-stage embryo transfers from January 1, 2012 to June 31, 2015 in the Reproductive Medicine Center of Wuhan General Hospital of Guangzhou Military Region. Based on the infertility etiologies of the patients, the 1003 cycles were divided into five groups： tubal infertility, polycystic ovary syndrome （PCOS）, endometriosis, male infertility, and unexplained infertility. The main outcome was the live birth rate. Two groups were set up based on the intervention： group A was given a GnRH agonist with exogenous estrogen and progesterone, and group B （control group） was given exogenous estrogen and progesterone only. The results showed that the baseline serum hormone levels and basic characteristics of the patients were not significantly different between groups A and B. The live birth rates in groups A and B were 41.67% and 29.29%, respectively （P〈0.05）. The live birth rates in patients with PCOS in groups A and B were 56.25% and 30.61%, respectively （P〈0.05）. The clinical pregnancy, implantation and on-going pregnancy rates showed the same trends as the live birth rates between groups A and B. The ectopic pregnancy rate was significantly lower in group A than in group B. We concluded that the live birth rate was higher and other clinical outcomes were more satisfactory with GnRH agonist co- treatment than without GnRH agonist co-treatment for frozen-thawed embryo transfer. The GnRH agonist combined with exogenous estrogen and progesterone worked for all types of infertility tested, especially for women with PCOS.
基金supported by the grants from Research and Innovation Project for Master Degree Candidates(105930903014)Guangxi Natural Science Foundation(06400150832043 and 0991042+3 种基金Guangxi Science and Technology Department)Research Foundation of Guangxi Education Department(200709LX075Guangxi Education and Research)Guangxi Large-scale Instrument Collaboration and Sharing Network Program
文摘[ Objective] To locate gonadotropin-releasing hormone （GnRH） in pituitary of Guangxi swamp buffaloes and to provide a theoretical ba- sis for cloning and sequence analysis of GnRH receptor gene. [ Method] GnRH in pituitary were immunohistochemically stained by avidin biotin complex method. The GnRH expression was analyzed with image system. The GnRH receptor gene was amplified by real-time PCR. [ Result] Many GnRH positive cells were detected in pars distalis of adenohypophysis. GnRH were distributed in cytoplasm but not in nuclei. No positive sig- nal was observed in neurohypophysis. In addition, the GnRH receptor gene, 920 bp in size, was amplified. [ Conclusion] A large number of GnRH and GnRH receptor were found in pars distalis of adenohypophysis, which indicates that anterior pituitary is an important tissue for functions of hypo- thalamus-pituitary-gonadal axis and other endocrine axes.
基金supported by a grant from TUBITAK,project No.110S381
文摘The hypothalamic Arg-Phe-amide-related peptides, gonadotropin-inhibitory hormone and orthologous mammalian peptides of Arg-Phe-amide, may be important regulators of the hypothalamus-pituitary-gonadal reproductive axis. These peptides may modulate the effects of kisspeptins because they are presently recognized as the most potent activators of the hypothalamus-pituitary-gonadal axis. However, their effects on gonadotropin-releasing hormone neurons have not been investigated. In the current study, the GT1-7 cell line-expressing gonadotropin-releasing hormone was used as a model to explore the effects of Arg-Phe- amide-related peptides on kisspeptin activation. Intracellular calcium concentration was quantified using the calcium-sensitive dye, fura-2 acetoxymethyl ester. Gonadotropin-releasing hormone released into the medium was detected via enzyme-linked immunosorbent assay. Results showed that 100 nmol/L kisspeptin-10 significantly increased gonadotropin-releasing hormone levels （at 120 minutes of exposure） and intracellular calcium concentrations. Co-treatment of kisspeptin with 1 μmol/L gonadotropin-inhibitory hormone or 1 μmol/L Arg-Phe-amide-related peptide-1 significantly attenuated levels of kisspeptin-induced gonadotropin-releasing hormone but did not affect kisspeptin-induced elevations of intracellular calcium concentration. Overall, the results suggest that gonadotropin-inhibitory hormone and Arg-Phe-amide-related peptide-1 may have inhibitory effects on kisspeptin-activated gonadotropin-releasing hormone neurons independent of the calcium signaling pathway.
文摘Gonadotropin-releasing hormone （GnRH） neurons in the preoptic area may undergo morphological changes during the pubertal period when their activities are upregulated. To clarify the regulatory mechanism of puberty onset, this study aimed to investigate the morphological changes of GnRH neurons in the preoptic area of GnRH-enhanced green fluorescent protein transgenic rats. Under confocal laser microscopy, pubertal GnRH neurons exhibited an inverted Y distribution pattern. Prepubertal GnRH neurons were generally unipolar and bipolar, and were distinguished as smooth type cells with few small processes or irregular type cells with many spine-like processes in the proximal dendrites. The number of GnRH neurons in the preoptic area and spine-like processes were increased during the course of reproductive maturation. There was no significant difference between male and female rats. Immunofluorescence staining revealed synaptophysin punctae close to the distal end of GnRH neurons, indicating that some presynaptic terminals may form a synaptic linkage with these neurons.
文摘Kisspeptin is essential for activation of the hypothalamo-pituitary-gonadal axis. In this study, we established gonadotropin-releasing hormone/enhanced green fluorescent protein transgenic rats. Rats were injected with 1, 10, or 100 pM kisspeptin-10, a peptide derived from full-length kisspeptin, into the arcuate nucleus and medial preoptic area, and with the kJsspeptJn antagonist peptJde 234 into the lateral cerebral ventricle. The results of immunohistochemical staining revealed that pulsatile luteinizing hormone secretion was suppressed after injection of antagonist peptide 234 into the lateral cerebral ventricle, and a significant increase in luteinizing hormone level was observed after kisspeptin-10 injection into the arcuate nucleus and medial preoptic area. The results of an enzyme-linked immunosorbent assay showed that luteinizing hormone levels during the first hour of kisspeptin-10 infusion into the arcuate nucleus were significantly greater in the 100 pM kisspeptin-10 group than in the 10 pM kisspeptin-10 group. These findings indicate that kisspeptin directly promotes gonadotropin-releasing hormone secretion and luteinizing hormone release in gonadotropin-releasing hormone/enhanced green fluorescent protein transgenic rats. The arcuate nucleus is a key component of the kisspeptin-G protein-coupled receptor 54 signaling pathway underlying regulating luteinizing hormone pulse secretion.
基金supported by grants from the Scientific Research Development Fund of Peking University People’s Hospital(No.RDY2020-27)Clinical Medicine Plus X-Young Scholars Project,Peking University,and the Fundamental Research Funds for the Central Universities(No.PKU2021LCXQ020).
文摘Objective It is well known that a dual trigger treatment can improve clinical outcomes of in vitro fertilization(IVF)in high or normal ovarian responders.However,it is not clear whether dual triggering also benefits patients with diminished ovarian reserve(DOR).The aim of this study was to investigate whether a dual trigger treatment of gonadotropin-releasing hormone(GnRH)agonist combined with human chorionic gonadotropin(hCG)for final follicular maturation improves the cumulative live birth rate(CLBR)during the GnRH-antagonist cycle in patients with DOR.Methods This retrospective study included patients with DOR who received a GnRH-antagonist protocol during IVF and intracytoplasmic sperm injection(IVF-ICSI)cycles at Peking University People’s Hospital from January 1,2017 through December 31,2017.Oocyte maturation was triggered by GnRH combined with hCG(n=110)or hCG alone(n=71).Embryos were transferred on the third day after oocyte retrieval or during a subsequent freeze-thaw cycle.Patients were followed up for 3 years.Results The dual trigger treatment did not affect CLBR,which is an overall determinant of the success rate of assisted reproductive technology(ART).Women in the dual trigger group had significantly higher rates of fertilization than those in the hCG group(90.1%vs.83.9%,P=0.040).Conclusion Dual trigger with GnRH agonist and hCG did not improve CLBR in patients with DOR,but did slightly improve fertilization rate,oocyte count,and embryo quality.
文摘目的比较卵巢子宫内膜异位囊肿(OEC)剔除术后辅以地诺孕素与促性腺激素释放激素激动剂(GnRH-a)治疗后患者疼痛和疾病复发率的差异。方法本研究为随机对照试验。依据随机硬币投掷法,将2020年5月至2022年4月西电集团医院妇产科符合OEC剔除术治疗标准的113例患者分为GnRH-a组(61例)和地诺组(52例)。GnRH-a组年龄(35.38±4.49)岁;病程(3.28±1.04)年;囊肿大小6.00(5.00,8.00)cm;美国生殖医学学会(American Society for Reproductive Medicine,ASRM)分期:Ⅰ~Ⅱ期30例,Ⅲ~Ⅳ期31例。地诺组年龄(35.52±4.61)岁;病程(3.52±1.06)年;囊肿大小6.00(5.00,8.00)cm;ASRM分期:Ⅰ~Ⅱ期26例,Ⅲ~Ⅳ期26例。从剔除术后首次月经来潮的第1天开始,GnRH-a组采用腹前壁皮下注射醋酸亮丙瑞林进行辅助治疗,3.75 mg/次,4周一次;地诺组口服地诺孕素片进行辅助治疗,2 mg/次,每天一次。两组均持续治疗24周。比较两组视觉模拟评分法(VAS)评分、不良反应、复发率和治疗满意度。采用独立样本t检验、非参数Wilcoxon检验、Mann-Whitney U检验、χ2检验进行统计学分析。结果用药24周后,地诺组痛经、慢性盆腔痛和性交痛VAS评分均低于GnRH-a组[0.50(0,2.00)分比1.00(0,3.00)分,1.00(0,3.00)分比2.00(1.00,4.00)分,0(0,2.00)分比1.00(0,2.00)分](Z=2.396、2.669、2.929,均P<0.05)。GnRH-a组和地诺组不良反应发生率和停药后12个月复发率比较[14.75%(9/61)比5.77%(3/52),8.20%(5/61)比1.92%(1/52)],差异均无统计学意义(χ2=2.378、2.197,均P>0.05)。地诺组治疗总满意度高于GnRH-a组[94.23%(49/52)比81.97%(50/61)](χ2=3.889,P<0.05)。结论相较于GnRH-a,OEC剔除术后辅以地诺孕素能有效缓解患者疼痛,预防疾病复发,获得更高的治疗满意度。
基金This study was supported by a grant from the National Natural Science Foundation of Key Program （No. 31230047）.
文摘Background： Luteal support is a key to patients undergoing in vitro fertilization and embryo transfer （IVF-ET） with gonadotropin-releasing hormone （GnRH）-antagonist protocol. This study aimed to compare the effect between vaginal progesterone （VP） and intramuscular progesterone （IMP） with GnRH-antagonist protocol alter IVF-ET. Methods： A total of 1760 patients （18 years ≤ age ≤35 years） undergoing IVF-ET with GnRH-antagonist protocol were studied retrospectively between September 2014 and August 2015 in Peking University Third Hospital. In the patients, 1341 patients received VP （VP group） and 419 patients received IMP （IMP group） as luteal support. We compared clinical outcomes between these two groups. The primary objective of the study was the live birth rate. Measurement data between the two groups were conducted using independent samples t-test. The variables in line with non-normal distribution were expressed as median （p25 and p75） and were compared using nonparametric Mann. Whitney U-test. Results： Live birth rate in VP group was 38.55%, significantly higher than that in the IMP group, which was 30.79% （x^2 = 8.287, P= 0.004）. The clinical intrauterine pregnancy rate and implantation rate in VP group were also significantly higher than those in the IMP group （clinical intrauterine pregnancy rate 47.35% vs. 41.29%, x^2= 4.727, P = 0.030： implantation rate 30.99% vs. 25.26%, x^2=14.546, P 〈 0.001）. Any statistically significant differences in ectopic pregnancy and abortion rates between two groups were not observed. Conclusion： Luteal support with VP had better clinical outcomes for young women undergoing IVF-ET with GnRH-antagonist protocol.
基金This work was supported by the grants from the National Natural Science Foundation of China （No. 30571938） and the ＂985＂ Project of the Peking University Health Science Center （No. 985-2-015-24）.Acknowledgments： We thank Prof. Dan Cacsire Castillo Tong, Molecular Oncology Group of Department of Obstetrics and Gynecology at Medical University of Vienna, for the helpful advice on revision of the manuscript and English wording.
文摘Background Type I gonadotropin-releasing hormone （GnRH-l） agonists have been applied for the treatment of steroid-dependent tumors such as breast carcinoma, ovarian cancer and prostatic carcinoma. But the mechanism has not been clarified yet. There are few reports about the treatment of endometrial carcinoma using GnRH-l agonists. Type II GnRH （GnRH-ll） is a new subtype of GnRH. Our aim was to investigate the effects of GnRH-l agonists and GnRH-ll on estrogen receptor-negative human endometrial carcinoma cells and the effect from phosphatase and tensin homolog gene （PTEN） to them.Methods A lentiviral vector-mediated RNAi method was used to establish a PTEN-negative HEC-1A cell clone （HEC-1A-ND）. MTT and flow cytometry were used to detect the cell proliferation, cell cycle and apoptosis of HEC-1A, HEC-1A-NC and HEC-1A-ND cells after treatment with GnRH-l agonist Triptorelin （10-11 mol/L to 10-5 mol/L） or GnRH-ll （10-11 mol/L to 10-5 mol/L）. Western blotting was used to detect AKT and ERK1/2 activation after treatment with different concentrations of Triptorelin or GnRH-ll for 30 minutes in the above mentioned three kinds of cells. Results Triptorelin and GnRH-ll induced apoptosis and inhibited proliferation of HEC-1 A, HEC-1A-ND and HEC-1A-NC in a dose-dependent manner. This effect was augmented in HEC-1 A-ND cells in which PTEN gene was knocked-down. Furthermore, Triptorelin and GnRH-ll inhibited the AKT and ERK activity in HEC-1 A-ND cells.Conclusions Triptorelin and GnRH-ll can promote apoptosis rate and inhibit cell proliferation of estrogen receptor-negative endometrial carcinoma cells in a dose-dependent manner. PTEN gene can inhibit the effects of Triptorelin or GnRH-ll on human endometrial carcinoma cells.
文摘Background Recently, conservative surgery is acceptable in young patients with borderline ovarian tumor and ovarian cancer. The preservation of these patients＇ future fertility has been the focus of recent interest. This study aimed to observe the effect of gonadotropin-releasing hormone agonists （GnRHa） cotreatment during chemotherapy in borderline ovarian tumor and ovarian cancer patients. Methods Sixteen patients who were treated with fertility preservation surgery for borderline ovarian tumor and ovarian cancer and then administered GnRHa during chemotherapy in Peking University People＇s Hospital from January 2006 to July 2010 were retrospectively analyzed. This group was compared with a control group of 16 women who were treated concurrently with similar chemotherapy （n=5） without GnRHa or were historical controls （n=11）. The disease recurrence, the menstruation status and reproductive outcome were followed up and compared between the two groups. Results There were no significant differences between both groups regarding age, body weight, height, marriage status, classification of the tumors, stage of the disease, as were the cumulative doses of each chemotherapeutic agent. One （1/16） patient in the study group while 2 （2/16） patients in the control group relapsed 2 years after conclusion of the primary treatment （P 〉0.05）. All of the 16 women in the study group compared with 11 of the 16 patients in the control group resumed normal menses 6 months after the termination of the treatment （P 〈0.05）. There were 4 spontaneous pregnancies in the study group while 2 in the control group, all of the neonates were healthy. Conclusions GnRHa administration before and during chemotherapy in borderline ovarian tumor and ovarian cancer patients who had undergone fertility preservation operation may bring up higher rates of spontaneous resumption of menses and a better pregnancy rate. Long-term follow up and large scale clinical studies are required.
文摘Background Ovarian hyperstimulation syndrome （OHSS） is one of the most life-threatening complications of assisted reproduction treatments. Gonadotropin-releasing hormone antagonists （GnRHanta） are thought to be effective in preventing this complication, and some clinical trials have found lower incidences of OHSS in patients treated with GnRHanta. Our aim was to investigate the effects of GnRHanta on vascular permeability and the expression of vascular endothelial growth factor （VEGF） and its receptors in a rat model of OHSS. Methods An immature early OHSS rat model was established. Three ovarian stimulation protocols were used： pregnant mare serum gonadotropin/human chorionic gonadotropin （hCG） alone, with a GnRHanta, or with a gonadotropin-releasing hormone agonists （GnRHa）. Blood and tissue samples were collected at 48 hours after hCG administration. Vascular permeability was evaluated by measuring the Evans-Blue content of extravasated peritoneal fluids. The expression of VEGF and its receptors, including fit-1 and KDR, were detected by reverse transcriptase-polymerase chain reaction and Western blotting. Results Treatment with both a GnRHanta and a GnRHa resulted in significant reductions in serum estradiol and peritoneal vascular permeability, as well as decreased ovarian expression of VEGF and its two receptors. However, GnRHanta treatment caused a greater reduction in serum estradiol concentrations, and in VEGF receptor mRNA expression than GnRHa. There were no significant reductions in the expression of VEGF or its receptors in extra-ovarian tissues, including the liver, lungs and peritoneum. Conclusion Our results reveal that GnRHanta are more potent than GnRHa in preventing early OHSS through down-regulation of the expression of VEGF and its receptors in hyperstimulated ovaries.
文摘Background： Delayed puberty can result either from constitutional delay of growth and puberty （CDP） or idiopathic hypogonadotropic hypogonadism （IHH）. Gonadotropin-releasing hormone （GnRH） stimulation test has been generally accepted as a current method for diagnosing delayed puberty. The objective of this research was to assess the cut-offvalues and the efficacy of GnRH stimulation test in the diagnosis of delayed puberty in both males and females. Methods： A study of 91 IHH, 27 CDP patients, 6 prepubertal children, and 20 pubertal adults was undertaken. Blood samples were obtained at 0, 30, 60, and 120 rain after GnRH administration and the levels of luteinizing hormone （LH） and follicle-stimulating hormone （FSH） were rneast, red. For each paralneter, the sensitivities and specificities were estimated, and the receiver operating characteristic （ROC） curves were constructed. Resulis： The ROC curves indicated that a serunl basal LH 〈0.6 IU/L or peak LH 〈9.74 IU/L resulted in moderate sensitivity （73.8% or 80.0%） and specificity （90.9% or 86.4%） in the diagnosis of HH in males. Serum basal LH 〈0.85 IU/L or basal FSH 〈2.43 IU/L resulted in moderate sensitivity （80.0% or 100.0%） and specificity （75.0% or 50.0%） in the diagnosis of HH in females. Conclusions： Our data suggest that isolated use of the gonadorelin stimulation test is almost sufficient to discriminate between HH and CDP in males, but unnecessary in females. The most useful predictor is serum basal or peak LH to differentiate these two disorders in males, but serum basal LH or FSH in females.
