ANDROGEN BLOCKADE AND SENSITIVITY OF THE GNRH PULSE GENERATOR

该子项目是利用 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来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 PCOS妇女GnRH脉冲发生器对雌二醇和孕酮抑制的敏感性降低。 雄激素水平升高似乎介导了这种敏感性降低，因为雄激素受体阻断剂氟替卡松可以恢复敏感性。 青少年高雄激素血症被认为是PCOS的前兆，并且患有高雄激素血症的青春期女孩的一个子集与患有PCOS的成年人相似，下丘脑对孕酮的敏感性降低。 我们假设氟替卡松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。 将在口服雌二醇和孕酮7天之前和之后，对已接受氟吡格雷预治疗28天的高雄激素性青春期女孩的LH（GnRH）脉冲频率进行评估。 作为第7天孕酮水平的函数的LH脉冲频率的百分比变化的斜率将用作下丘脑孕酮敏感性的量度。 将用氟替卡松预治疗的女孩的下丘脑孕酮敏感性与未接受氟替卡松的历史对照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.