•Fig. 44.20 Two-cellmodelforsteroidogenesisinthedominantfollicle.Top panel: MG,muralgranulosa;T,theca.(ModifiedfromWhiteBA,PorterfieldSP.Endocrine Physiology. 4thed.Philadelphia:Mosby;2013.)LHreceptor LH LDLR and HDLR-mediated uptake FSH receptor Expression of LH receptor Expression of CYP19 (aromatase) LH receptor FSH Expression and activation of StAR protein Expression of steroidogenic enzymes Acetate Cholesterol Pregnenolone Progesterone 17 (OH) Progesterone Androstenedione Testosterone Thecal cell Granulosa cell StAR protein CYP11A1 CYP17 CYP17 CYP19 CYP19 EstroneAndrostenedione Testosterone Estradiol-17˜3˜-HSD 17˜-HSD 17˜-HSD 17˜-HSD Blood vessel Basal lamina MG A a C C T
The thecal cells of large antral follicles produce significant amounts of androstenedione and less testosterone. Androgens are converted to estradiol-17β by the granulosa cells (
Fig. 44.20 ). At this stage, FSH stimulates proliferation of granulosa cells and induces the expression of CYP19 (aromatase) required for estrogen synthesis. Additionally the mural granulosa cells of the large antral follicles produce increasing amounts of inhibin during the early follicular phase. Low levels of estrogen and inhibin negatively feed back on FSH secretion, thereby contributing to selection of the follicle with the most FSH-responsive cells.
As already discussed, at the end of a previous menstrual cycle, a crop of large (2–5 mm) antral follicles (see
Fig.
44.17 ) are recruited by a rise in FSH to begin rapid gonadotropin-dependent development. The total number of recruited follicles in both ovaries can be as high as 20 in a younger woman (<33 years old) but rapidly declines at older ages. The number of recruited follicles is reduced to the ovulation quota (one in humans) by the process of selection. As FSH levels decline the rapidly growing follicles progressively undergo atresia until one follicle is left. Generally the largest follicle with the most FSH receptors of the recruited crop becomes the dominant follicle. Selection occurs during the early follicular phase. By midcycle the dominant follicle becomes a large preovulatory follicle that is 20 mm in diameter and contains about 50 million granulosa cells by the midcycle gonadotropin surge.
The Gamete
The oocyte is competent to complete meiosis I but remains arrested in the dominant follicle until the LH surge. Growth of the oocyte continues but at a slower rate until the oocyte reaches a diameter of about 140 µm by ovulation (i.e., ≈20 times the diameter of an erythrocyte).
The newly selected follicle emerges as a significant steroidogenic “gland.” Ovarian steroidogenesis requires both theca and granulosa cells. As discussed earlier, thecal cells (see