ANDROGEN RECEPTOR CAG REPEAT POLYMORPHISM & HYPOTHALAMIC SEX STEROID SENSITIVITY

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。 青少年高雄激素血症似乎是成人多囊卵巢综合征(PCOS)的先兆。患有多囊卵巢综合征的成年女性对孕激素抑制GnRH搏动性的敏感性降低。雄激素似乎在调节孕激素敏感性方面发挥了作用，因为使用雄激素阻滞剂氟他胺可以恢复敏感性。我们发现，一些高雄激素血症的青春期女孩对孕激素抑制GnRH搏动性的敏感性降低，而另一些女孩尽管雄激素水平相当，但仍保持敏感性。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，这表明可能是遗传原因。雄激素受体CAG重复长度多态性赋予不同的雄激素受体反式激活活性。雄激素受体CAG重复长度多态性在不同种族和民族中的分布存在差异。 我们建议在对孕激素抑制GnRH搏动性敏感和不敏感的高雄激素血症青春期女孩中检测雄激素受体CAG重复长度。这一结果将使我们能够确定雄激素受体CAG重复序列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中发挥作用。

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.