Female sexuality: modulation by estrogen and androgen

女性性行为：雌激素和雄激素的调节

基本信息

批准号：
6601142
负责人：
Kim Wallen
金额：
$ 36万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-06-01 至 2006-05-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): 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 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 interest in reproductively prime ovariectomized female monkeys. The hypothesis will be tested that chronic progestin therapy reduces or eliminates the effectiveness of therapies that reinstate female sexual interest without progestin. These therapies will also be compared on their effects on neuroendocrine function. These studies will markedly increase our understanding of the role that ovarian steroids play in modulating women's sexuality.

描述（由申请人提供）：该假设被调查，卵巢雌激素的神经作用刺激了女性性兴趣，并且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。使用内分泌功能和行为的恒河猴模型进行了三个项目，研究了女性性启动的荷尔蒙基础。项目I研究了整个月经周期中女性的性启动，比较了用雄激素受体阻滞剂（Flutamide）或雌激素受体阻滞剂（Tamoxifen）治疗的正常周期中女性性启动的发生。这将阐明雄激素或雌激素是否神经起作用以调节女性性动机。项目II检验了新的假设，即SHBG通过这些类固醇对SHBG的不同亲和力调节可生物利用的雌激素和雄激素。该项目使用猴子替代疗法的猴子模型在手术清除卵巢后生殖蛋白女性，并检验了慢性雌二醇（E2）停止刺激女性性兴趣的假说，因为雌激素是由SHBG序列的。它进一步研究了与雌激素相比，对SHBG的亲和力明显高的雄激素是否可以通过取代SHBG结合的雌二醇来增加自由雌二醇，从而明显高于SHBG。仅在慢性E2治疗期间和慢性E2和注射DHT或E2注射时，将观察到接受慢性雌二醇治疗的卵巢切除雌性。同时使用雌激素或DHT施用氟他胺或他莫昔芬将区分由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进行研究。 III项目研究了慢性雌激素的常见人类荷尔蒙替代疗法，还是有或没有并发孕激素的慢性雌激素加上睾丸激素，是否可以恢复女性在生殖产生产卵的雌性猴子中的性兴趣。该假设将检验，慢性孕激素治疗可降低或消除恢复女性性兴趣而没有孕激素的疗法的有效性。这些疗法还将与它们对神经内分泌功能的影响进行比较。这些研究将显着提高我们对卵巢类固醇在调节妇女性行为中发挥的作用的理解。