Effect of Hyperinsulinemia on Hyperandrogenism in PCOS

Several lines of evidence suggest that the compensatory hyperinsulinemia associated with insulin resistance is critical to the pathogenesis of hyperandrogenism in PCOS. In in vitro cultures of isolated human ovarian thecal cells, ovarian testosterone biosynthesis stimulated by insulin was fourfold greater in cells from women with PCOS than those of normal women, and in a dose-response study insulin stimulated thecal androgen production at physiological concentrations (3). This stimulation of testosterone production was almost fully prevented by antibody blockade of the insulin receptors. This suggests that insulin stimulates ovarian thecal testosterone biosynthesis via activation of its homologous receptor.

Insulin also decreases circulating levels of sex hormone-binding globulin (SHBG), the primary circulating binding protein for testosterone (4). Because of testosterone's high-affinity binding to SHBG, lower SHBG levels translate to increased levels of free and bioavailable testosterone to target tissues. In addition, insulin may also influence secretory dynamics of gonadotropins by the pituitary, resulting in further stimulation of ovarian androgen production (5-7).

In vivo data also suggest that hyperinsulinemia is associated with an increased level of circulating testosterone in PCOS. When pancreatic insulin secretion was suppressed in women with PCOS by diazoxide, both serum total and free testosterone levels decreased (8). However, diazoxide's suppression of insulin release in healthy normal women did not result in changes in serum testosterone levels (9). Hence, hyperinsulinemia seems to play a role in hyperandrogenemia in PCOS, and women with PCOS may be more susceptible than normal women to stimulation of ovarian androgen production by insulin.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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