Granulosa cells of polycystic ovaries: are they normal or abnormal?

Understanding whether granulosa cells are normal or abnormal in women with polycystic ovary syndrome (PCO) could have clinical importance. For this purpose, we compared the ability of normal and PCO granulosa cells to synthesize oestrogen and progesterone in vitro in response to follicle stimulating hormone (FSH) and/or insulin-like growth factor-I (IGF-I). The normal granulosa cells were from a 7 mm dominant follicle from a women with regular menstrual cycles. The PCO granulosa cells were from 5-7 mm follicles of three patients who had classical PCO. Several interesting points emerge from the comparison: in each PCO patient there was a high level of bioactive FSH in the follicular microenvironment (greater than or equal to 5 mIU/ml; greater than or equal to 250 ng/ml). This is paradoxical because the concentration of steroids in follicular fluid suggests that PCO follicles are highly atretic and therefore should not contain detectable FSH activity. The capacity to secrete progesterone when challenged with a maximally effective dose of FSH and/or IGF-I, was markedly reduced (8- to 10-fold) in PCO compared to normal granulosa cells. This is in sharp contrast to the oestradiol responses which were much the same for PCO and normal granulosa cells. Also, the time course and dose-response effects of FSH showed some major differences between normal and PCO cells, that is, PCO cells lost their capacity to produce oestradiol when treated continuously with a maximally effective dose of FSH. They were also significantly more sensitive to FSH and failed to become more sensitive to IGF-I when treated with FSH.(ABSTRACT TRUNCATED AT 250 WORDS)