Estradiol production by granulosa cells of normal and polycystic ovaries: relationship to menstrual cycle history and concentrations of gonadotropins and sex steroids in follicular fluid

Abstract

The underlying cause of anovulation in polycystic ovary syndrome is unknown. Circulating levels of immuno- and bioactive FSH are within the normal range, and the follicles contain measurable levels of bioactive FSH. The aim of this study was to compare estradiol (E2) production in response to FSH by granulosa cells from normal ovaries with those from polycystic ovaries derived from both anovulatory (anovPCO) and ovulatory subjects (ovPCO). Intrafollicular levels of immunoactive FSH, E2, and androstenedione in follicles of less than 12 mm were also measured. Follicular fluid steroid concentrations were obtained from 41 pairs of normal ovaries and 23 pairs of polycystic ovaries (8 anovPCO and 15 ovPCO). In size-matched follicles from each group there were no significant differences in follicular fluid FSH or E2 concentrations, but androstenedione levels were significantly higher in 5- to 11-mm follicles from ovPCO than in corresponding follicles from normal ovaries. Dose responses to FSH were determined in granulosa cells derived from 9 pairs of normal ovaries, 7 anovPCO, and 8 ovPCO. Cells from anovPCO produced 6- to 10-fold more E2 in response to FSH than normal cells, although there was no significant difference in the ED50 values. The response in cells from ovPCO was reduced compared to normal, but this difference did not reach significance. In summary, as judged by their FSH and E2 contents, polycystic ovaries do not have a higher proportion of atretic follicles than normal. Indeed, cells from anovPCO are hyperesponsive to FSH in vitro. This could be explained by stimulation of aromatase in vivo by either paracrine or, more probably, by endocrine factors, of which insulin is an arguable candidate.

Testosterone-induced downregulation of anti-Müllerian hormone expression in granulosa cells from small bovine follicles

“…The ovarian physiology in PCOS patients differs in many aspects from normal ovarian physiology. PCOS preantral follicles show a prolonged survival [25], granulosa cells respond prematurely to LH [26] and display increased aromatase activity [27]. Moreover, the chronic exposure to androgens may have long-term effects that have not been addressed in our study.…”

Anti-Müllerian hormone reduces follicle sensitivity to follicle-stimulating hormone in human granulosa cells

“…The ovaries removed from each patient were seen by a pathologist before a portion of each was taken to the laboratory for dissection. Morphology and ovulatory status were assigned as previously published (15).The timing of surgery was random.…”

Polycystic ovary syndrome and its developmental origins

“…An endogenous inhibitor of estrogen synthesis likely exists in small estrogen-deplete PCOS follicles with sufficient bioactive FSH [52] because cultured granulosa cells from these follicles are hyperresponsive to FSH in vitro [53,54]. New sonographic ovarian studies in PCOS patients show that the number of 2-5 mm follicles positively correlates with serum T levels, while that of 6-9 mm follicles negatively correlates with fasting serum insulin and T levels, as well as body mass index (BMI) [55].…”

“…Enhanced theca cell androgen biosynthesis [28,29], increased initiation of primordial follicle growth [43] and exaggerated granulosa cell responsiveness to FSH [54] are features of follicle development in PCOS patients undergoing in vitro fertilization (IVF). With more retrieved oocytes and cleaved embryos available to select for embryo transfer, PCOS patients undergoing IVF often achieve a clinical pregnancy rate comparable to that of similarly treated normal women [94][95][96].…”