NEUROENDOCRINE MEDIATION OD SOCIALLY INDUCED ANOVULATION

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。该项目于2005年7月启动，使用雌性恒河猴模型研究社会诱导的无排卵或功能性下丘脑无排卵的神经内分泌机制和遗传脆弱性。第一项研究检验了以下假设：与长等位基因纯合子（n = 20）女性相比，编码5-羟色胺再摄取转运蛋白（SERT; n = 20）基因的短变异等位基因纯合子或杂合子女性将显示低代谢表型。携带短等位基因的女性的体重和体脂质量指数显著低于携带长等位基因的女性（体重：7.89 <$0.24 vs 9.08 <$0.35 kg; BMI：13.66 <$0.39 vs 15.24 <$0.54）。携带短等位基因的女性也显示出胰岛素水平较低的低代谢状态的证据（34.4 <$7.3与38.6 <$7.1 ng/ml），T3（158.9 <$11.9对比171.3 <$6.0 ng/ml），T4 4.7 <$0.2对比5.3 <$.4 ng/ml）和更高水平的生长激素释放肽（10.3 <$1.3对比8.0 <$1.0 pg/ml）。此外，与长等位基因的女性相比，具有sort等位基因的女性显示出更高的无排卵发生率（20%对0%）。 接下来的研究将确定社会地位如何加剧这种对代谢失调的遗传脆弱性，从而影响生育能力。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project was initiated in July 2005 to study the neuroendocrine mechanisms and genetic vulnerability responsible for socially induced anovulation or functional hypothalamic anovulation using a female rhesus monkey model. The first study tested the hypothesis that females homozygous or heterozygous for the short variant allele for the gene that encodes the serotonin reuptake transporter (SERT; n = 20) would show a hypometabolic phenotype compared to females homozygous for the long allele (n = 20). Females with the short allele had significantly lower body weights and body fat mass indices than females with the long allele (weight: 7.89 ¿ 0.24 vs. 9.08 ¿ 0.35 kg; BMI: 13.66 ¿ 0.39 vs. 15.24 ¿ 0.54). Females with the short allele also show evidence of a hypometabolic condition having lower levels of insulin (34.4 ¿ 7.3 vs.38.6 ¿ 7.1 ng/ml), T3 (158.9 ¿ 11.9 vs. 171.3 ¿ 6.0 ng/ml), and T4 4.7 ¿ 0.2 vs. 5.3 ¿ .4 ng/ml) and higher levels of ghrelin (10.3 ¿ 1.3 vs. 8.0 ¿ 1.0 pg/ml). Furthermore, females with the sort allele showed a higher incidence of anovulation compared to females with the long allele (20% vs. 0%). Upcoming studies will define how social status exacerbates this increased genetic vulnerability to metabolic dysregulation to compromise fertility.