Insulin Stimulates Testosterone Biosynthesis by Human Thecal Cells from Women with Polycystic Ovary Syndrome by Activating Its Own Receptor and Using Inositolglycan Mediators as the Signal Transduction System¹

TLDR

The study aimed to determine whether insulin stimulates testosterone production in PCOS thecal cells via its own receptor and inositolglycan signaling. Thecal cells from PCOS women were isolated, cultured, and exposed to insulin, IGF‑I, and specific antibodies to dissect receptor and inositolglycan involvement. Insulin and IGF‑I stimulate thecal testosterone production, and blockade of the insulin receptor or inositolglycan antibodies abolishes this effect, indicating that inositolglycans mediate insulin‑induced testosterone biosynthesis in PCOS thecal cells.

Abstract

To determine whether insulin stimulates human ovarian testosterone production in the polycystic ovary syndrome by activating its own receptor and using inositolglycan mediators as the signal transduction system, thecal cells from polycystic ovary syndrome women were isolated and cultured. Insulin and insulin-like growth factor I stimulated thecal testosterone biosynthesis. Antibody blockade of the insulin receptor abolished insulin's stimulatory action, whereas effective antibody blockade of the insulin-like growth factor I receptor did not alter insulin's stimulation of thecal testosterone biosynthesis. A chiro-inositol containing glycan (INS-2) increased thecal testosterone biosynthesis. Preincubation of cells with an antiinositolglycan antibody (A23939 or alpha IGP) abolished insulin's stimulatory effect, but not that of hCG. These findings suggest that inositolglycans serve as the signal transduction system for insulin's stimulation of human thecal testosterone biosynthesis.