NEUROENDOCRINE MEDIATION OD SOCIALLY INDUCED ANOVULATION

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。本项目于2005年7月启动，目的是利用雌性恒河猴模型研究社会诱导无排卵或功能性下丘脑无排卵的神经内分泌机制和遗传易感性。第一项研究验证了一个假设，即编码5 -羟色胺再摄取转运体（SERT, n = 20）的短变异等位基因的女性纯合或杂合，与长等位基因的女性纯合（n = 20）相比，会表现出低代谢表型。携带短等位基因的女性体重和体脂质量指数明显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）。具有短等位基因的女性也表现出低代谢状况的证据，胰岛素水平较低（34.4 - 7.3 vs.38.6 - 7.1 ng/ml）， T3水平较低（158.9 - 11.9 vs. 171.3 - 6.0 ng/ml）， T4水平为4.7 - 0.2 vs. 5.3。4 ng/ml)和更高水平的胃饥饿素（10.3 ~ 1.3 vs. 8.0 ~ 1.0 pg/ml）。此外，具有排序等位基因的雌性比具有长等位基因的雌性表现出更高的无排卵发生率（20%比0%）。接下来的研究将确定社会地位如何加剧这种增加的遗传脆弱性，从而导致代谢失调，从而损害生育能力。

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.