ANDROGEN RECEPTOR CAG REPEAT POLYMORPHISM & HYPOTHALAMIC SEX STEROID SENSITIVITY

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。 青少年高雄激素血症似乎是成人多囊卵巢综合征（PCOS）的前兆。患有PCOS的成年女性对孕酮抑制GnRH脉动的敏感性降低。雄激素似乎在介导孕激素敏感性方面发挥作用，因为使用雄激素阻断剂氟替卡松可以恢复敏感性。 我们发现，一些高雄激素血症的青春期女孩显示降低敏感性孕酮抑制GnRH脉动，而其他人保持敏感性，尽管同等的雄激素水平。 所有保持孕激素敏感性的高雄激素血症女孩都是西班牙裔，提示可能的遗传病因。雄激素受体CAG重复长度多态性赋予可变的雄激素受体反式激活活性。雄激素受体CAG重复序列长度多态性在不同种族和民族中的分布不同。 我们建议检查雄激素受体CAG重复长度在高雄激素血症的青春期女孩和不敏感的孕酮抑制GnRH脉动。 这些结果将使我们能够确定雄激素受体CAG重复多态性是否在决定高雄激素血症神经内分泌效应的易感性方面发挥作用。

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. Adolescent hyperandrogenemia appears to be a precursor to adult polycystic ovary syndrome (PCOS). Adult women with PCOS have reduced sensitivity to progesterone inhibition of GnRH pulsatility. Androgens appear to play a role in mediating progesterone sensitivity, as sensitivity can be restored with the use of the androgen blocker flutamide. We have found that some hyperandrogenemic adolescent girls show reduced sensitivity to progesterone inhibition of GnRH pulsatility while others maintain sensitivity despite equivalent androgen levels. All of the hyperandrogenemic girls who maintained progesterone sensitivity were Hispanic, suggesting a possible genetic etiology. Androgen receptor CAG repeat length polymorphisms confer variable androgen receptor transactivation activities. The distribution of androgen receptor CAG repeat length polymorphism varies in different racial and ethnic groups. We propose to examine the androgen receptor CAG repeat length in hyperandrogenemic adolescent girls with and without sensitivity to progesterone inhibition of GnRH pulsatility. The results will allow us to determine whether androgen receptor CAG repeat polymorphisms play a role in determining susceptibility to the neuroendocrine effects of hyperandrogenemia.