PCOS is a disorder marked by excessive ovarian androgen production, but its etiology is unknown. Provocative ovarian testing involving markedly supraphysiologic LH stimuli have produced abnormal steroid responses in PCOS, leading to the theory that inherent abnormalities of ovarian steroidogenesis underlie PCOS. We propose to further explore this hypothesis in specific aim 1 by delineating ovarian steroid responses to physiologic LH stimuli, thus allowing the construction of LH-steroid dose-response curves in both normal women and women with PCOS. Consistent features of PCOS include persistent LH hypersecretion, insulin resistance/hyperinsulinemia, and hyperandrogenemia, and some or all of these factors may play a role in causing and/or perpetuating the abnormalities of ovarian steroidogenesis.
In specific aim 2, studies will investigate the relative roles of persistent LH hypersecretion, hyperinsulinemia, and ovarian hyperandrogenemia in the maintenance of abnormal ovarian steroid responses to LH in PCOS. The ovarian steroid response to physiologic LH stimulation will be examined 6 weeks after reduction of LH using the gonadotropin-releasing hormone agonist leuprolide; 6 weeks after reduction of hyperinsulinemia using metformin or rosiglitazone; and 6 weeks after androgen receptor blockade using flutamide. The results of these studies will help elucidate mechanisms involved in ovarian hyperandrogenemia in women with PCOS.
| McCartney, Christopher R; Bellows, Amy B; Gingrich, Melissa B et al. (2004) Exaggerated 17-hydroxyprogesterone response to intravenous infusions of recombinant human LH in women with polycystic ovary syndrome. Am J Physiol Endocrinol Metab 286:E902-8 |
| McCartney, Christopher R; Eagleson, Christine A; Marshall, John C (2002) Regulation of gonadotropin secretion: implications for polycystic ovary syndrome. Semin Reprod Med 20:317-26 |
