Theca Cell Function in Adolescents With Polycystic Ovary Syndrome (PCOS)

In women with polycystic ovary syndrome (PCOS), the cardinal physiological abnormality is excessive ovarian androgen production marked by increased serum testosterone (T) and androstenedione (A) levels. Studies to determine the alteration in ovarian steroidogenesis that lead to abnormal production of ovarian androgens have revealed increased CYP17 gene expression with accentuated 17-hydroxylase activity leading to exaggerated 17-hydroxyprogesterone (17P) responses to luteinizing hormone (LH) stimulation. In contrast, T and A responses did not distinguish between PCOS and normal women, although these androgens were clearly greater in the former compared to the latter group. As a result, 17P responsiveness has been employed to determine the functional capacity of the ovary to produce androgens. The stimulatory agents that have been used included GnRH agonist, Lupron, at a dose of 10 microgram per kilogram, or hCG at a dose of 10,000 IU. The investigators propose to conduct a study that will determine the pattern of androgen responsiveness to 25ucg of hCG after 24 hours in adolescents with PCOS, those with oligomenorrhea, and in normal controls. This will allow for a comparison of these adolescents' ovarian functional capacity to produce androgens.

In women with polycystic ovary syndrome (PCOS), the cardinal physiological abnormality is excessive ovarian androgen production marked by increased serum testosterone (T) and androstenedione (A) levels. Studies to determine the alteration in ovarian steroidogenesis that lead to abnormal production of ovarian androgens have revealed increased CYP17 gene expression with accentuated 17-hydroxylase activity leading to exaggerated 17-hydroxyprogesterone (17P) responses to luteinizing hormone (LH) stimulation. In contrast, T and A responses did not distinguish between PCOS and normal women, although these androgens were clearly greater in the former compared to the latter group. As a result, 17P responsiveness has been employed to determine the functional capacity of the ovary to produce androgens. The stimulatory agents that have been used included GnRH agonist, Lupron, at a dose of 10 microgram per kilogram, or hCG at a dose of 10,000 IU.We propose to conduct a study that will determine the pattern of androgen responsiveness to 25ucg of hCG after 24 hours in adolescents with PCOS, those with oligomenorrhea, and in normal controls. This will allow for a comparison of these adolescents' ovarian functional capacity to produce androgens.

PCOS, oligomenorrhea, irregular menses, hyperandrogenemia, elevated testosterone, adolescents, androgens, ovary, LH

Intervention: Each subject in the PCOS group will receive 1 mg of oral dexamethasone in the evening and return in the morning for an injection of 25ug of IV recombinant human chorionic gonadotropin. Subjects will also have blood drawn at times -0.5, 0, 0.5, and 24 hours after the injection of r-hCG for measurement of steroid hormones.

Intervention: Each subject in the Normal group will receive dexamethasone 1 mg orally in the evening and return the next morning for an injection of 25ug of IV recombinant human chorionic gonadotropin. Subjects will the have blood drawn at -0.5, 0, 0.5, and 24 hours after hCG injection for steroid hormone measurements.

Intervention: Each subject in the Oligomenorrhea group will receive dexamethasone 1 mg orally in the evening and return the next morning for an injection of 25ug of IV recombinant human chorionic gonadotropin. Subjects will the have blood drawn at -0.5, 0, 0.5, and 24 hours after hCG injection for steroid hormone measurements.

Each subject in each group will receive 1 mg of oral dexamethasone in the evening and return in the morning for an injection of 25ug of IV recombinant human chorionic gonadotropin. Subjects will also have blood drawn at times -0.5, 0, 0.5, and 24 hours after the injection of r-hCG for measurement of steroid hormones.

Each subject in each group will receive 1 mg of oral dexamethasone in the evening and return in the morning for an injection of 25ug of IV recombinant human chorionic gonadotropin (r-hCG). Subjects will also have blood drawn at times -0.5, 0, 0.5, and 24 hours after the injection of r-hCG for measurement of steroid hormones.

Inclusion Criteria: Normal CBC (Hemoglobin must be at least 11mg/dl) Normal renal and liver function tests Normal vital signs including normal blood pressure Exclusion Criteria: Pregnancy On oral contraceptives On insulin lowering drugs On anti-androgens (i.e., spironolactone, flutamide, finasteride, etc) On medications that will influence androgen metabolism or clearance On medications that will inhibit the cytochrome P450 enzyme system (Cimetidine, ketoconazole, etc)