Production of transforming growth factor-alpha by normal and polycystic ovaries.

The mechanism of anovulation in polycystic ovary (PCO) syndrome remains unknown. As circulating concentrations of FSH are apparently normal, and in vivo, granulosa cells from anovulatory PCO are hyperresponsive to FSH, it has been suggested that the lack of follicular development in anovulatory PCO is caused by overexpression of a paracrine growth factor that inhibits steroidogenesis. Epidermal growth factor and the structurally homologous transforming growth factor-alpha (TGF alpha) are suitable candidates for this role, but although the production of the latter has been demonstrated in the ovary, no comparison has been performed between the levels in normal ovaries and PCO. We compared the levels of TGF alpha in follicular fluid and in granulosa cell- and theca- and stroma-conditioned media from normal ovaries and PCO. TGF alpha was present in the range of 0.2-200 ng/mL in follicular fluid. There was a significant inverse correlation of TGF alpha with follicle size, with no differences between follicles from normal ovaries and PCO. Granulosa cell-conditioned medium contained concentrations of TGF alpha ranging from 0.1-200 ng/1000 cells. There was a wide range of concentrations in theca- and stroma-conditioned media, with levels varying from 0.2-100 ng/mg tissue and no consistent effect of LH. There were no significant differences between the levels from normal ovaries or PCO in medium conditioned by any compartment of the ovary. We conclude that the failure of folliculogenesis in PCO syndrome is not likely to be due to overproduction of TGF alpha by the ovary.