Insulin action in the normal and polycystic ovary.
Insulin has a stimulatory effect on steroidogenesis by granulosa cells of normal and polycystic ovaries and interacts with gonadotropins in an additive or, as in the case of LH, a synergistic manner. These actions seem to be mediated specifically by the insulin receptor rather than by cross-reaction with the type I IGF receptor, even in tissue obtained from women with PCOS with biochemical evidence of insulin resistance. The authors suggest that hyperinsulinemia makes a significant contribution to premature arrest of follicle growth, which is characteristic of anovulation in women with PCOS, and that the interaction of insulin with LH is a key element in this process. Insulin may also have a role in amplifying LH-induced androgen production by theca cells, which may help explain the prominence of symptoms of hyperandrogenism in obese subjects with PCOS. The results of recent clinical studies of insulin-sensitizing agents such as metformin and the thiazoladinedione troglitazone in PCOS have provided encouragement that improvement of insulin sensitivity and consequent lowering of circulating insulin levels by these agents may be of therapeutic value in the management of both anovulation and hirsutism.
Franks
S
S
Department of Reproductive Science and Medicine, Imperial College School of Medicine, St. Mary's Hospital, London, United Kingdom. s.franks@ic.ac.uk
Gilling-Smith
C
C
Watson
H
H
Willis
D
D
D004347:Drug Interactions; D005260:Female; D006065:Gonadotropins, Pituitary / Q000494:pharmacology; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D010053:Ovary / Q000187:drug effects* / Q000254:growth & development / Q000503:physiopathology*; D011085:Polycystic Ovary Syndrome / Q000503:physiopathology*; D011972:Receptor, Insulin / Q000502:physiology; D013799:Theca Cells / Q000187:drug effects
D006065:Gonadotropins, Pituitary; D007328:Insulin; D011972:Receptor, Insulin