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. Author manuscript; available in PMC: 2015 Sep 8.
Published in final edited form as: Fertil Steril. 2013 Mar 6;100(1):23–38. doi: 10.1016/j.fertnstert.2013.02.011

FIGURE 2.

FIGURE 2

Transition from primary to secondary/small antral follicles. Granulosa cells proliferate and follicles grow in response to multiple factors including activin, IGF-I, WNT4/5a, and FSH. The transcription factor FOXO1 impacts both follicle growth and follicle atresia (see the text for details). Consequently, as the distance between the oocyte and the theca layer is increased, theca cell production of androgens becomes more dependent on LH and possibly inhibin-α. Levels of AMH increase and negatively regulate FSH action in granulosa cells to prevent premature maturation. In lean PCOS patients, elevated LH and insulin levels increase theca cell androgen production, which enhances FSHR expression and premature differentiation of granulosa cells via induction of aromatase (CYP19a1), LH receptor (LHCGR), and other genes including RUNX2 (102). WNT4/5a may contribute to the enhanced actions of FSH to induce CYP19a1. Enhanced FSH actions override those of elevated AMH. Large gray circle: oocyte; red line: zona pellucida; small blue circles: granulosa cells; large blue circle: normal theca cells; green circle: PCOS theca. Oocyte factor and GDF9 signaling is denoted by green arrows; inhibin by the orange arrow; LH and androgen signaling by red arrows and letters; and insulin signaling by purple arrows and letters. Large blue arrow indicates continued normal follicular growth.