ANDROGEN BLOCKADE AND SENSITIVITY OF THE GNRH PULSE GENERATOR

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。 患有多囊卵巢综合征的妇女GnRH脉冲发生器对雌二醇和孕酮抑制的敏感性降低。雄激素水平的升高似乎介导了这种敏感性的下降，因为雄激素受体阻滞剂氟他胺可以恢复敏感性。青春期高雄激素血症被认为是多囊卵巢综合征的先兆，患有高雄激素血症的青春期女孩的一部分与患有多囊卵巢综合征的成年女孩一样，降低了下丘脑对孕酮的敏感性。我们假设氟他胺可以通过阻断雄激素的作用来恢复这些女孩的下丘脑孕酮敏感性。对已接受氟他胺预治疗28天的高雄激素性青春期女孩，在口服雌二醇和孕酮7天前和7天后评估促黄体生成素(GnRH)脉搏频率。黄体生成素脉冲频率随第7天孕酮水平变化的百分比斜率将被用来衡量下丘脑孕酮的敏感性。接受氟他胺预治疗的女孩对下丘脑孕酮的敏感性将与未接受氟他胺治疗的历史对照组的下丘脑孕酮敏感性进行比较。

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. Women with PCOS have decreased GnRH pulse generator sensitivity to suppression by estradiol and progesterone. Increased androgen levels appear to mediate this decrease in sensitivity, as sensitivity can be restored with the androgen receptor blocker flutamide. Adolescent hyperandrogenemia is thought to be a precursor of PCOS, and a subset of adolescent girls with hyperandrogenemia have decreased hypothalamic sensitivity to progesterone similar to their adult counterparts with PCOS. We hypothesize that flutamide will restore hypothalamic progesterone sensitivity in these girls by blocking the effects of androgens. LH (GnRH) pulse frequency will be assessed before and after 7 days of oral estradiol and progesterone in hyperandrogenic adolescent girls who have been pretreated for 28 days with flutamide. The slope of the percentage change in LH pulse frequency as a function of Day 7 progesterone level will be used as a measure of hypothalamic progesterone sensitivity. Hypothalamic progesterone sensitivity in the girls pretreated with flutamide will be compared to hypothamic progesterone sensitivity in historic controls who did not receive flutamide.