Steroidogenesis in human polycystic ovary

Polycystic ovarian disease (PCOD) is a heterogenous condition with a broad clinical and pathologic spectrum that may reflect the effects of diverse etiologic factors. Depending on the diagnostic data available from patients, various steroidogenic enzyme blocks have been postulated, mostly implicating higher-than-normal production of circulating delta 4-androstenedione, testosterone, and, in some cases, dehydroisoandrosterone. These high levels of androgens, because of their peripheral conversion to estrogens, lead to inappropriate secretion of gonadotropins in PCOD. Whatever may be the etiologic factors, the common entity is a polycystic ovary. Such an ovary contains preantral follicles, few antral follicles, many atretic follicles, and follicular and degenerative cysts. The follicles lack a sufficient number of mature granulosa cells to produce enough estrogens. On the other hand, there is a hypertrophy of stromal and thecal tissue continuously producing androgens. The steroid analysis of the follicular fluid obtained from the cystic follicles of the polycystic ovary revealed high concentration of delta 4-androstenedione and absence of, or only minute amounts of, estrogens. Early studies of biosynthesis of steroids in the polycystic ovary demonstrated conversion of progesterone mainly to androgens. Arising from these observations was the suggestion that an aromatase enzyme block existed. That suggestion was corroborated in the findings of higher-than-normal circulating androgens in PCOD. Later, other partial enzymatic blocks of beta-hydroxydehydrogenase and 17-hydroxylase were also suggested. However, it is known that the therapies such as wedge resection, administration of FSH, or FSH/LH (Pergonal) and LHRH leads to ovulation and, in most cases, normal cyclicity in the polycystic ovary. The knowledge gained from these therapies clearly indicates that the enzymatic blocks or abnormal steroidogenesis in the polycystic ovary may be due to the absence of proper gonadotropin response, and the main defect may be at the hypothalamic-pituitary axis. In PCOD with hyperinsulinemia, insulin and IGF-I have been implicated in the production of androgens by the polycystic ovary. The mechanism of the action of insulin or IGF-I is not yet known, however.