FEMALE SEXUALITY: MODULATION BY ESTROGEN AND ANDROGEN

女性性欲：雌激素和雄激素的调节

• 批准号: 7349200
• 负责人: Kim Wallen
• 金额: $ 4.01万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-09 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7349200
• 关键词: androgens; estradiol; estrogens; female; motivation

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. The hypothesis is investigated that female sexual interest is stimulated by the neural actions of ovarian estrogens and that androgens regulate the bioavailability of these estrogens through interactions with sex hormone binding globulin (SHBG). Three projects, using a rhesus monkey model of endocrine function and behavior, investigate the hormonal basis of female sexual initiation. Project I investigates sexual initiation in females across the menstrual cycle, comparing the occurrence of female sexual initiation in a social group context during normal to cycles treated with an androgen receptor blocker (flutamide) or an estrogen receptor blocker (tamoxifen). This will clarify whether androgens or estrogens act neurally to modulate female sexual motivation. Project II tests the novel hypothesis that SHBG regulates bioavailable estrogens and androgens through these steroids¿ different affinities for SHBG. This project uses a monkey model of hormonal replacement therapy for reproductively prime females after surgical removal of their ovaries and tests the hypothesis that chronic estradiol (E2) ceases to effectively stimulate female sexual interest as estrogen is sequestered by SHBG. It further investigates whether an androgen, 5a-dihydrotestosterone (DHT), with a markedly higher affinity for SHBG than estradiol, can acutely and rapidly reinstate female sexual interest by increasing free estradiol by displacing SHBG-bound estradiol. Ovariectomized females receiving chronic estradiol treatment mimicking mid follicular estradiol levels will be observed for sexual initiation during chronic E2 treatment alone and following chronic E2 and an injection of DHT or E2. Concurrent administration of flutamide or tamoxifen with the estrogen or DHT will discriminate between behavioral changes resulting from the activation of neural androgen or estrogen receptors. The effects of these treatments on neuroendocrine function will also be investigated. Project III investigates whether common human hormonal replacement therapies of chronic estrogen, or chronic estrogen plus testosterone with or without concurrent progestin can reinstate female sexual interested in reproductively prime ovariectomized female monkeys. The hypothesis will be tested that chronic progestin therapy reduces or eliminates the effectiveness therapies that reinstate female sexual interest without progestin. These therapies will also be compared on their effects on neuroendocrine function Theses studies will markedly increase our understanding of the role that ovarian steroids play in modulating women¿s sexuality.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。研究假设认为，女性性兴趣是由卵巢雌激素的神经作用刺激的，雄激素通过与性激素结合球蛋白（SHBG）的相互作用来调节这些雌激素的生物利用度。三个项目使用恒河猴内分泌功能和行为模型，研究女性性起始的激素基础。项目 I 研究女性在整个月经周期的性起始，比较正常社会群体背景下女性性起始的发生率与使用雄激素受体阻滞剂（氟他胺）或雌激素受体阻滞剂（他莫昔芬）治疗的周期。这将澄清雄激素或雌激素是否通过神经作用来调节女性性动机。项目 II 测试了新的假设，即性激素结合球蛋白 (SHBG) 通过这些类固醇（对性激素结合球蛋白的不同亲和力）调节生物可利用的雌激素和雄激素。该项目使用猴子模型对生殖能力较好的雌性动物在手术切除卵巢后进行激素替代疗法，并测试以下假设：由于雌激素被性激素结合球蛋白 (SHBG) 隔离，慢性雌二醇 (E2) 不再有效刺激雌性性兴趣。它进一步研究了雄激素 5a-二氢睾酮 (DHT) 与性激素结合球蛋白 (SHBG) 的亲和力明显高于雌二醇，是否可以通过取代与性激素结合球蛋白 (SHBG) 结合的雌二醇来增加游离雌二醇，从而迅速恢复女性的性兴趣。接受模拟卵泡中期雌二醇水平的慢性雌二醇治疗的卵巢切除女性将在单独长期E2治疗期间以及在慢性E2和注射DHT或E2之后观察性开始。氟他胺或他莫昔芬与雌激素或双氢睾酮同时给药将区分由神经雄激素或雌激素受体激活引起的行为变化。还将研究这些治疗对神经内分泌功能的影响。项目 III 研究慢性雌激素的常见人类激素替代疗法，或慢性雌激素加睾酮联合或不联合孕激素是否可以恢复处于生殖期卵巢切除的雌性猴子的性兴趣。将检验以下假设：长期孕激素治疗会降低或消除在不使用孕激素的情况下恢复女性性兴趣的有效疗法。还将比较这些疗法对神经内分泌功能的影响。这些研究将显着增加我们对卵巢类固醇在调节女性性欲中所起作用的理解。