Ovarian steroid biosynthetic pathways

Outline of the organization of the major steroid biosynthetic pathways in the small antral follicle of the ovary, depicted according to the two-gonadotropin, two-cell model of ovarian steroidogenesis. LH stimulates androgen formation within theca cells via the steroidogenic pathway common to the gonads and adrenal glands. FSH regulates estradiol biosynthesis from androgen by granulosa cells. Long-loop negative feedback of estradiol on gonadotropin secretion does not suppress LH at follicular phase levels of estradiol, nor do modest elevations of androgen suppress LH. Androgen formation in response to LH appears to be modulated by intraovarian feedback, mainly at the levels of 17-hydroxylase and 17, 20-lyase, both of which are activities of cytochrome P450c17. The quantitative importance of androstenedione formation from 17-hydroxyprogesterone (thin grey arrow) in the intact follicle is unknown. Androgens and estradiol inhibit (minus signs) and inhibin, insulin, and insulin-like growth factors (IGF) stimulate (plus signs) 17-hydroxylase and 17, 20-lyase activities. The steroidogenic enzymes appear in red.