FEMALE SEXUALITY: MODULATION BY ESTROGEN AND ANDROGEN

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 研究的假设是，女性的性兴趣是由卵巢雌激素的神经行为刺激，雄激素通过与性激素结合球蛋白（SHBG）的相互作用调节这些雌激素的生物利用度。 三个项目，使用恒河猴模型的内分泌功能和行为，调查女性性启动的激素基础。项目I调查了女性在整个月经周期中的性启动，比较了在正常周期与雄激素受体阻滞剂（氟氯噻嗪）或雌激素受体阻滞剂（他莫昔芬）治疗周期中女性在社会群体背景下的性启动发生率。 项目II测试了SHBG通过这些类固醇对SHBG的不同亲和力调节生物可利用的雌激素和雄激素的新假设。 该项目使用激素替代治疗的猴子模型，用于手术切除卵巢后的生殖初期女性，并测试慢性雌二醇（E2）不再有效刺激女性性兴趣的假设，因为雌激素被SHBG隔离。 它进一步研究了雄激素，5 α-双氢睾酮（DHT），具有显着更高的亲和力比雌二醇的SHBG，是否可以通过增加游离雌二醇取代SHBG结合雌二醇急性和快速恢复女性的性兴趣。 观察接受模拟卵泡中期雌二醇水平的长期雌二醇治疗的卵巢切除女性在单独的长期E2治疗期间以及在长期E2和注射DHT或E2之后的性启动。 氟替卡松或他莫昔芬与雌激素或双氢睾酮同时给药可区分由神经雄激素或雌激素受体激活引起的行为变化。项目III研究了慢性雌激素或慢性雌激素加睾酮（伴或不伴雌激素）的常见人类激素替代疗法是否可以恢复雌性对生育初期卵巢切除雌性猴的性兴趣。该假设将被测试，慢性前列腺素治疗减少或消除的有效性疗法，恢复女性的性兴趣没有前列腺素。还将比较这些疗法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的作用的理解。

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 cycles vs cycles treated with an androgen receptor blocker (flutamide) or an estrogen receptor blocker (tamoxifen). 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 are 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. 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.