Ovarian and adrenal function in polycystic ovary syndrome.
Androgens are secreted by both the ovaries and adrenal glands in response to their respective trophic hormones LH and ACTH. Androgens in women are not specifically under negative feedback control by these pituitary hormones because they are by-products of estradiol and cortisol secretion. Rather, androgen secretion seems to be regulated mostly by intraglandular mechanisms. Functional ovarian hyperandrogenism is found in about 70% of patients with PCOS. It is characterized by excessive secretion of 17-hydroxyprogesterone in response to GnRH agonist or hCG stimulation. Failure of dexamethasone to suppress plasma free testosterone normally in the presence of normal adrenocortical suppression is also typical. Functional adrenal hyperandrogenism is found in about half of patients with PCOS. It is most often characterized by moderately increased secretion of the 17-ketosteroid DHEA in response to ACTH. The most likely cause of the excessive androgen secretion by both glands seems to be abnormal regulation (dysregulation) of the 17-hydroxylase and 17,20-lyase activities of P-450c17, the rate-limiting step in androgen biosynthesis. There are also subtle generalized disturbances of steroid metabolism, including tendencies toward excessive estrogen and cortisol secretion. The cause of dysregulation of steroidogenesis is unknown. The hyperinsulinemia that is compensatory for resistance to the glucose-metabolic effect of insulin seems to have a role in many cases. In most cases, intrinsic intraovarian or intra-adrenal autocrine or paracrine regulatory mechanisms are most likely malfunctioning.
Rosenfield
R L
RL
Department of Pediatrics, Pritzker School of Medicine, University of Chicago, Illinois.
D000311:Adrenal Glands / Q000503:physiopathology*; D000728:Androgens / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D010053:Ovary / Q000503:physiopathology*; D011085:Polycystic Ovary Syndrome / Q000503:physiopathology*
D000728:Androgens