Rj. Auchus et al., THE REGULATION OF HUMAN P450C17 ACTIVITY - RELATIONSHIP TO PREMATURE ADRENARCHE, INSULIN-RESISTANCE AND THE POLYCYSTIC-OVARY-SYNDROME, Trends in endocrinology and metabolism, 9(2), 1998, pp. 47-50
The polycystic ovary syndrome (PCOS) is characterized by hyperandrogen
ism and insulin resistance, but the connection between these two featu
res has been unclear. Androgen synthesis is regulated in part by the r
atio of the 17 alpha-hydroxylase and 17,20 lyase activities of P450c17
. Three separate lines of evidence show that the ratio of lyase to hyd
roxylase activity is regulated by electron flow from P450 oxidoreducta
se. Lyase activity and androgen synthesis are particularly dependent o
n the serine phosphorylation of P450c17. Serene phosphorylation of the
insulin receptor beta chain causes insulin resistance, and some PCOS
women have hyperphosphorylated receptors. We hypothesize that an overa
ctive serine/threonine kinase hyperphosphorylates both the insulin rec
eptor and P450c17 in PCOS, accounting for the characteristic insulin r
esistance and hyperandrogenism of this disease.