FEMALE SEXUALITY: MODULATION BY ESTROGEN AND ANDROGEN

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 研究的假设是，女性的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，使用内分泌功能和行为的恒河猴模型，研究女性性行为的荷尔蒙基础。项目I调查了女性在整个月经周期中的性启动，将正常周期中在社会群体背景下女性性启动的发生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)治疗的周期进行了比较。这将澄清雄激素或雌激素是否在调节女性性动机方面起到中性作用。项目II测试了新的假设，即SHBG通过这些类固醇对SHBG的不同亲和力来调节生物可用雌激素和雄激素。这个项目使用了一个猴子模型，在手术切除卵巢后，对生殖能力最好的女性进行荷尔蒙替代疗法，并测试了这样的假设，即随着雌激素被SHBG隔离，慢性雌二醇(E2)不再有效地刺激女性的性兴趣。它进一步研究了一种雄激素，5a-双氢睾酮(DHT)，它对SHBG的亲和力明显高于雌二醇，是否可以通过取代SHBG结合的雌二醇来增加游离雌二醇，从而迅速而迅速地恢复女性的性兴趣。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的女性，将在单独的慢性E2治疗期间以及在慢性E2和注射DHT或E2之后观察性行为的启动。同时给予氟他胺或他莫昔芬和雌激素或DHT，将区分神经雄激素或雌激素受体激活引起的行为变化。这些治疗对神经内分泌功能的影响也将被调查。项目III调查了常见的人类激素替代疗法慢性雌激素，或慢性雌激素加睾酮与或不与同时孕激素一起使用，是否可以恢复女性对生殖最好的去卵巢雌性猴子的性欲。这一假设将得到检验，即慢性黄体酮治疗会减少或消除恢复女性性欲而不使用黄体酮的有效疗法。这些疗法还将比较它们对神经内分泌功能的影响。这些研究增加了我们对卵巢类固醇在调节女性性行为中所起作用的理解。

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 neutrally 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 increase our understanding of the role that ovarian steroids play in modulating female sexuality.