Leutinizing hormone/choriogonadotropin receptor and follicle stimulating hormone receptor gene variants in polycystic ovary syndrome

Purpose

Previous studies identified follicle-stimulating hormone receptor (FSHR) and luteinizing hormone/choriogonadotropin receptor (LHCGR) genes as polycystic ovary syndrome (PCOS) susceptibility loci, which was dependent on the racial/ethnic background of studied population. We investigated the association of genetic variants in FSHR and LHCGR with PCOS in Bahraini Arab women.

Methods

A retrospective case–control study, involving 203 women with PCOS, and 211 age- and ethnically-matched control women. FSHR and LHCGR genotyping was done by allelic exclusion method (real-time PCR).

Results

Significantly lower frequencies of heterozygous LHCGR rs7371084 and FSHR rs11692782 genotype carriers were seen between women with PCOS vs. controls, and increased frequency of heterozygous homozygous LHCGR rs4953616 genotype carriers were detected between women with PCOS compared to control women. Limited linkage disequilibrium was noted among LHCGR and FSHR SNPs, and 2 blocks were constructed: the first (Block 1) spanning 61 kb contained the six tested LHCGR SNPs, and the second (Block 2) spanning 298 kb contained four of the five tested FSHR SNPs. Higher frequency of LHCGR GTCAAG haplotype was seen in women with PCOS compared to controls; the frequencies of the remaining LHCGR haplotypes, and all FSHR haplotypes were similar between cases and controls.

Conclusion

This is the first study to confirm the association of novel LHCGR (rs7371084, rs4953616) and FSHR (rs11692782) SNPs with PCOS. The differential association of LHCGR and FSHR variants with PCOS confirms the racial/ethnic contribution to their association with PCOS.

     

The Asn680Ser polymorphism of the follicle stimulating hormone receptor gene and ovarian cancer risk: a meta-analysis

Purpose

The purpose of this study was to conduct a meta-analysis to assess the association between FSHR Asn680Ser polymorphism and ovarian cancer susceptibility.

Methods

A literature search was conducted in PubMed, Embase and the China National Knowledge Infrastructure (CNKI) for all relevant studies published up to September 2013. The pooled odds ratios (ORs) with the corresponding 95 % confidence intervals (95 % CIs) were calculated to evaluate the association.

Results

Four case–control studies including 474 ovarian cancer cases and 659 controls met the inclusion criteria. The pooled analyses showed that FSHR Asn680Ser polymorphism was associated with the risk of ovarian cancer (Ser vs Asn: OR = 1.295, 95 % CI 1.057–1.498, P = 0.01; Ser/Ser + Asn/Ser vs Asn/Asn: OR = 1.611, 95 % CI 1.027–2.528, P = 0.038). Subgroup analyses by ethnicity (Caucasian and Asian) further revealed significant associations among Asians (Ser vs Asn: OR = 1.386, 95 % CI 1.066–1.802, P = 0.015; Ser/Ser + Asn/Ser vs Asn/Asn: OR = 1.893, 95 % CI 1.329–2.689, P = 0.000) but not Caucasians. There was no obvious risk of publication bias.

Conclusions

The meta-analysis suggests that FSHR Asn680Ser polymorphism may be a risk factor for ovarian cancer in Asians. Due to the limited quantity of the included studies, further studies are needed to validate the above conclusions.     

GnRHa降调节后月经第3天的FSH/LH比值预测卵巢的反应性

目的探索促性腺激素释放激素激动剂（GnRHa）降调节后月经第3天的血卵泡刺激素（FSH）/黄体生成素（LH）比值在控制性超排卵（COH）中预测卵巢反应性的价值。方法用全自动酶联免疫分析法检测439个COH周期的基础血卵泡刺激素值和GnRHa降调节后月经第3天的FSH、LH值，分析Gn-RHa降调节后月经第3天的FSH/LH比值与成熟卵泡数、临床妊娠率等的关系；并比较FSH/LH比值、基础血卵泡刺激素、降调节后月经第3天的FSH值与成熟卵泡数的关系；同时按FSH/LH比值将439个周期分为四组：FSH/LH≤1，13，分析各组之间年龄、促性腺激素用量、成熟卵泡数、FSH、LH、受精数、卵裂数、临床妊娠率等的差异。结果GnRHa降调后FSH/LH比值与GnRHa降调节后月经第3天的FSH值与成熟卵泡数均成显著性负相关（r=-0.368；r=-0.219）；基础血卵泡刺激素与成熟卵泡数成不显著性负相关（r=-0.160）。FSH/LH比值对临床妊娠率有显著性影响（P=0.012）。在卵巢低反应组和正常反应组，FSH/LH比值具有显著性差异（P=0.016）。另外，在四组中，2〈FSH／LH≤3组的成熟卵泡数、临床妊娠率等显著高于其他三组。结论GnRHa降调节后血卵泡刺激素（FSH）／黄体生成素（LH）比值用于预测卵巢的反应性较血卵泡刺激素更敏感，可以用于作为判断COH结果的预测指标。     

超排卵周期卵巢的反应性与卵泡颗粒细胞中卵泡刺激素受体表达的关系

目的探讨超排卵周期卵巢的反应性与颗粒细胞中卵泡刺激素受体(FSHR)表达的关系。方法采用蛋白印迹法,测定因输卵管性不孕或者男性因素不孕的60例不孕症患者的卵泡颗粒细胞FSHR蛋白的水平;采用电化学发光法测定血清雌二醇峰值。根据超排卵周期中发育卵泡数,将60例患者分为卵巢低反应组(20例)、卵巢中反应组(20例)及卵巢高反应组(20例),比较各组FSHR蛋白表达水平,并分析FSHR表达水平与卵泡数、雌二醇峰值的相关性。结果(1)卵巢低反应组、卵巢中反应组及卵巢高反应组的FSHR蛋白表达分别为0·19±0·07、0·34±0·16及0·45±0·18,3组比较,差异均有统计学意义(P<0·001);卵泡数分别为(2·5±0·5)、(7·9±1·9)及(21·6±3·8)个,3组比较,差异均有统计学意义(P<0·01);雌二醇峰值分别为3441、7864及22486pmol/L,3组比较,差异有统计学意义(P<0·01)。(2)3组患者超排卵周期颗粒细胞FSHR表达水平与卵泡数及雌二醇峰值均呈显著正相关关系(rs=0·52及0·71,P<0·01)。结论超排卵周期中,卵巢的反应性与颗粒细胞FSHR蛋白表达有关,FSHR表达水平的高低反映不同的卵巢反应类型。     

Effects of luteinizing hormone and follicle stimulating hormone on the developmental competence of porcine preantral follicle oocytes grown in vitro

Background There has been controversy over the role of FSH in the regulation of preantral follicle development. LH is a survival and differentiation factor that increases oocyte maturation in FSH-supplemented cultures of mouse preantral follicles. However, little information exists on the action of LH and FSH in the developmental competence of porcine preantral follicle oocytes in vitro. Materials and methods Porcine preantral follicles were cultured for 3 days in the presence or absence of FSH or LH. Oocytes from these follicles were then matured, fertilized in vitro, and embryos were cultured. Estradiol secretion and histological analysis of cultured follicles were also carried out. Results FSH or combined LH and FSH significantly enhanced follicular growth compared to LH alone or the controls. Combined LH and FSH treatment of preantral follicles significantly increased the percentage (59 ± 5%) of oocytes competent to undergo cleavage to the two-cell stage after fertilization. A significant effect was seen on oocyte competence to develop from the two-cell to the blastocyst stage (30 ± 6%) compared to FSH alone treatment (45 ± 7 and 14 ± 5%, respectively). The amount of estradiol on days 2 and 3 of culture was significantly higher in follicles cultured with FSH (48.75 ± 17, 70.5 ± 14 pg/ml) or combined LH and FSH (63.25 ± 16, 72.5 ± 12 pg/ml) than that cultured with the untreated controls (16 ± 10, 5.66 ± 4 pg/ml). Conclusions The results indicated that FSH is essential for the in vitro growth of porcine preantral follicles, estradiol secretion, and for oocytes to acquire competence to resume meiosis and undergo fertilization and embryonic development. LH with FSH treatment of porcine preantral follicles can improve the quality of oocytes by promoting growth and a higher frequency of embryonic development.     

Temporal coupling of luteinizing hormone and follicle stimulating hormone secretion in polycystic ovary syndrome

The aim of this study was to assess the luteinizing hormone (LH) and follicle stimulating hormone (FSH) pulsatile secretion and their temporal relation (concordance) in subjects with polycystic ovary syndrome (PCOS). Fifteen subjects were included in the study (age 17–30 years ,body mass index (BMI) 19.38–33.46 kg/m²). For the LH and FSH determinations ,blood sampling started at 23.00 and lasted for 6 h with an intersample interval of 10 min. Pulse analysis was carried out using the PulsDetekt program. LH/FSH pulse concordance was calculated using the specific concordance index. Gonadotropin co-pulsatility was found in six subjects who were significantly younger than the others (median 18.5 vs. 22.5 years ,p = 0.036). BMI ,hirsutism grade ,insulin sensitivity ,estradiol ,progesterone, testosterone ,prolactin ,cortisol and results obtained from the pulsatility analysis did not significantly differ between the groups. A serum cortisol concentration was correlated with the increased LH/FSH lag time (ρ = 0.851 ,p = 0.036) all subjects were included. In conclusion ,two distinct LH/FSH secretory patterns were found in PCOS patients ,manifested by the presence or absence of the concordance of gonadotropin secretion. In the group where LH/FSH co-pulsatility was present ,correlation was found between the serum cortisol and the LH/FSH lag. We also confirmed the finding of previous studies that LH and FSH secretion are regulated by two different mechanisms.     

Selective inhibition by danazol of follicle stimulating hormone during the luteal phase.

In each of six healthy, normally menstruating women, serum oestradiol, progesterone, basal and post luteinizing hormone releasing hormone (LHRH) gonadotrophin measurements were made during the luteal phase of a normal cycle and in a subsequent cycle in which 800 mg of danazol was given daily from the fifth day after the presumptive date of ovulation. No differences in the serum oestradiol, progesterone, or basal gonadotrophin levels were detected, but there was a selective impairment of the follicle stimulating hormone response to LHRH. The implications of these findings are discussed.     

Temporal coupling of luteinizing hormone and follicle stimulating hormone secretion in polycystic ovary syndrome.

The aim of this study was to assess the luteinizing hormone (LH) and follicle stimulating hormone (FSH) pulsatile secretion and their temporal relation (concordance) in subjects with polycystic ovary syndrome (PCOS). Fifteen subjects were included in the study (age 17-30 years, body mass index (BMI) 19.38-33.46 kg/m2). For the LH and FSH determinations, blood sampling started at 23.00 and lasted for 6 h with an intersample interval of 10 min. Pulse analysis was carried out using the PulsDetekt program. LH/FSH pulse concordance was calculated using the specific concordance index. Gonadotropin co-pulsatility was found in six subjects who were significantly younger than the others (median 18.5 vs. 22.5 years, p = 0.036). BMI, hirsutism grade, insulin sensitivity, estradiol, progesterone, testosterone, prolactin, cortisol and results obtained from the pulsatility analysis did not significantly differ between the groups. A serum cortisol concentration was correlated with the increased LH/FSH lag time (p = 0.851, p = 0.036) all subjects were included. In conclusion, two distinct LH/FSH secretory patterns were found in PCOS patients, manifested by the presence or absence of the concordance of gonadotropin secretion. In the group where LH/FSH co-pulsatility was present, correlation was found between the serum cortisol and the LH/FSH lag. We also confirmed the finding of previous studies that LH and FSH secretion are regulated by two different mechanisms.     

Effect of deprivation of endogenous follicle stimulating hormone on rat epididymis: a histological evaluation

The growth and function of the epididymis are regulated by testosterone produced by Leydig cells in the testes. In the present study it was observed that neutralization of endogenous follicle stimulating hormone (FSH) in immature rats using a highly specific antiserum to ovine FSH resulted in changes in the histology of the epididymis along with a decrease (50-60%) in its weight compared with the normal serum-treated controls. These changes were observed in both rat and monkey epididymis without any decrease in serum testosterone, on which epididymis is known to be dependent. A detailed study was therefore carried out on the effects of deprivation of FSH or testosterone on the histology of epididymis. The changes in epididymal histology following FSH deprivation included a decrease in the size of the tubule lumen in the rat as well as in the adult male bonnet monkey in which the antiserum against ovine FSH was raised. Intensive vacuolization and uneven surface of the luminal epithelium was also observed. In contrast, the effect of deprivation of testosterone support by way of administration of LH antiserum or fiutamide resulted in a decrease in the size of the lumen and degenerative changes. These results suggest that cauda epididymidis is a target for FSH action.     

Anti-Mullerian hormone and antral follicle count as predictors for embryo/oocyte cryopreservation cycle outcomes in breast cancer patients stimulated with letrozole and follicle stimulating hormone

Purpose  

To predict embryo/oocyte cryopreservation cycle (ECC) outcomes in breast cancer patients stimulated with letrozole and follicle stimulating hormone for fertility preservation based on observed anti-mullerian hormone (AMH) levels and antral follicle counts (AFC).     

卵泡刺激素多肽修饰的纳米粒制备及体外靶向性研究

目的 制备卵泡刺激素多肽修饰的纳米粒,并探讨其体外靶向性.方法 用免疫细胞化学法检测人肝癌细胞BEL-7402、人卵巢上皮性癌细胞SKOV-3和Caov-3中卵泡刺激素受体的表达.合成卵泡刺激素β链第81～95个氨基酸片段,并与纳米粒共价连接.通过细胞形态学和流式细胞技术进行多肽和纳米粒的靶向性检测.结果 制备的纳米粒直径为100 nm左右,Zeta电位大约为-25 mV.BEL-7402和SKOV-3细胞不表达卵泡刺激素受体,而Caov-3细胞的卵泡刺激素受体呈阳性表达.Caov-3细胞对卵泡刺激素多肽修饰的纳米粒的摄取能力为4.17±0.86,显著强于SKOV-3细胞的2.30±0.21,两者比较,差异有统计学意义(P<0.05).卵泡刺激素多肽修饰后,转运纳米粒的能力也显著增加,Caov-3细胞摄取卵泡刺激素多肽修饰纳米粒为4.17±0.86,而摄取纳米粒为0.41±0.32,两者比较,差异也有统计学意义(P<0.05),且随着时间延长和浓度增加而增强.结论 卵泡刺激素多肽修饰的纳米粒对卵泡刺激素受体阳性的卵巢上皮性癌细胞具有良好的靶向性,可能的机制为受体介导的特异性内吞作用.     

Anti-Mullerian hormone is a better marker than inhibin B,follicle stimulating hormone,estradiol or antral follicle count in predicting the outcome of in vitro fertilization

Objective  

The present study aims to compare anti-Mullerian hormone (AMH) with other ovarian reserve markers and to find a cut-off value of AMH for predicting ovarian response towards controlled ovarian hyperstimulation in an in vitro fertilization (IVF) program.