My previous article described the basic theory behind follicular growth.With that basic theory we can look at what is can happen when hormones and receptors don’t work properly. The following information comes from the article “The reproductive phenotype in polycystic ovary syndrome” by R Jeffrey Chang.I have changed some of the wording to simplify concepts, but if you want to read the article the in its’ originality go to:http://www.nature.com/ncpendmet/
1) Follicles Unable to Fully Mature. Normal follicle development involves pre-antral growth of the primordial follicle (containing an immature oocyte surrounded by a single layer of flat granulosa cells) to the more advanced stages of primary and secondary follicle development.During the transition between stages there is an increasing oocyte maturity and greater numbers of granulosa cells. In PCOS, normal follicular growth occurs up to the mid-antral stage of development, after which maturation ceases and the follicles begin to degenerate as granulosa cells die and dwindle in number. As the follicle starts to die, there is progressive accumulation of follicular fluid that results in the expansion of it. As the follicle enlarges, the granulosa cell layer of the follicle becomes progressively degenerative while the entire structure collects fluid and appears as a thin-walled cyst. Despite these degenerative changes, granulosa cells remain active and produce significant steroids (ie: fluids) until they eventual die. The theca cell layer that surrounds the follicle is considerably larger than that found in normal follicles and is responsible for increased androgen production, which results in more fluid to collect in the follicle. Why PCOS follicles cannot fully mature and cells starts die is not completely understood.It could be related to improper signaling of cellular death or receptors for follicular growth are missing or not functioning.
2) Too Many Pre-antral and Antral Follicles Another distinction of PCO is the increase in the numbers of growing pre-antral and antral follicles compared with those of the normal ovary. Little is known of the process that leads to multiple follicle recruitment. Whether the ovaries are endowed with a greater number of follicles, whether the rate of entry into the growing pool is increased or whether the rate of programmed cell death is decelerated has not been determined. Recent studies have suggested that anti-mullerian hormone (AMH) might be, in part, responsible for the increased follicle population in PCO. AMH, an exclusive product of granulosa cells of growing pre-antral and small-antral follicles, seems to control the advancement of follicle maturation.Its expression in growing pre-antral follicles of PCO is decreased compared with that of normal ovaries, resulting in less signaling to stop the advancement of too many follicles.Interestingly, women with PCOS have circulating AMH levels that are elevated compared with those of normal women; however, this might reflect the increased numbers of growing pre-antral and small-antral follicle population in PCO.
3.Problems with Androgens A.Defective Theca Cells Currently, evidence suggests that theca cells of women with PCOS have a defect and produce excessive amounts of androgens. Theca cells have been found to over produce ovarian androgens due to increased enzyme activities compared with theca cells from normal women.These results are consistent with studies in women with PCOS that demonstrated enhanced responsiveness to key androgen enzymes to stimulation by FSH/LH.Furthermore, it has been shown that, in PCOS, the response to human chorionic gonadotropin (HCG) was far more sensitive compared with normal women following suppression of FSH/LH by a GnRH agonists. This finding supports the idea that there is an abnormality in theca cells producing excessive amounts of androgens. B.Too Much LH Studies have shown women with PCOS that LH-induced theca cells produce androgens in equal amount to the secretion of LH.Research has found elevated LH levels positively correlate with increased circulating testosterone. In addition, in women who have PCOS and are treated with GnRH agonists, elevated LH levels are reduced or eliminated with a corresponding reduction in circulating androgen levels and hair growth.Increased secretion of LH might thus be pivotal in amplifying the production of excess androgen. C.Normal LH, Excessive Androgens and Insulin In some women with PCOS, serum LH levels are normal, which suggests that other factors can contribute to excessive androgen production. The most notable of these factors is insulin. Receptors for insulin have been localized to the theca cells in both normal women and patients with PCOS, plus insulin appears to active receptors in the ovary, besides the follicle.Studies of normal human theca tissue have demonstrated that insulin is capable of enhancing androgen production in response to LH as well as independently stimulating androgen production from other parts of the ovary. In theca cells from women with PCOS, insulin was shown to aggressively increase androgen production. Hyperinsulinemia is, nevertheless, linked to hyperandrogenemia in women with PCOS. In such women, hyperinsulinemia (induced either directly or indirectly) has not been associated with increases in serum androgen levels.The reduction of hyperinsulinemia in women with PCOS who are treated with insulin-lowering drugs is, however, associated with significant decreases of serum androgen levels without corresponding changes in LH levels; this observation indirectly suggests a role for insulin in LH-stimulated androgen synthesis.