Steroidogenic abnormalities in ovarian theca cells in polycystic ovary syndrome

The cellular mechanisms underlying excess ovarian androgen production in patients with polycystic ovary syndrome (PCOS) are presently unknown. Examination of the steroid biosynthesis by theca interna cells isolated from ovaries of normal women and ovaries from women with PCOS has recently advanced our understanding of the steroidogenic abnormalities that result in increased androgen biosynthesis in PCOS. In the past few years, the combined data derived from studies utilizing freshly isolated and propagated theca cells have established that both progestin and androgen biosynthesis are increased in theca cells obtained from PCOS ovaries. This increase in steroid biosynthesis results from selectively increased cholesterol side-chain cleavage (CYP11A), 3β-hydroxysteroid dehydrogenase type II (HSD3B2) and 17α-hydroxylase (CYP17) gene expression. The finding that increased androgen biosynthesis is a stable characteristic of propagated PCOS theca cells maintained in long-term culture has provided new opportunities to examine the molecular and cellular basis for increased ovarian androgen biosynthesis in patients with PCOS. By characterizing the regulatory systems mediating both metabolic and steroidogenic processes in normal and PCOS theca cells, it is anticipated that new information will be obtained that will provide insight into the relations between insulin resistance, hyperinsulinemia, and hyperandrogenemia in patients with PCOS