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.

该主题是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构是针对该中心的，这不是调查人员的机构。该假设的研究是，卵巢逃生剂的神经作用刺激了女性的性兴趣，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逃生的生物利用度。使用内分泌功能和行为的恒河猴模型进行了三个项目，研究了女性性倡议的马基础。项目I研究了整个月经周期中女性的性倡议，将女性性倡议在正常情况下的发生与用雄激素受体阻滞剂（Flutamide）或雌激素受体阻滞剂（Tamoxifen）治疗的周期进行了比较。这将阐明雄激素或雌激素是否中立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的不同亲和力来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外科手术去除卵巢后，以生殖性雌性，并检验了慢性雌二醇（E2）停止有效刺激女性性兴趣的假说，因为雌激素被SHBG隔离。它进一步研究了雄激素，5A二氢睾丸激素（DHT）是否比雌二醇高明显高的SHBG亲和力，可以通过取代SHBG结合的雌二醇来增加自由雌二醇，从而急性迅速地恢复女性性兴趣。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型女性。同时使用雌激素或DHT施用氟氨酰胺或他莫昔芬将区分由神经元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质量的卵巢雌性猴子中的性行为。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有效疗法。这些疗法还将在它们对神经内分泌功能的影响方面进行比较，这将显着提高我们对卵巢类固醇在调节女性性行为中起作用的作用的理解。