Follicular maturation and atresia--possible role of intraovarian regulatory factors.

In addition to the gonadotrophins, factors known to be present or produced within the ovary are also involved in the regulation of follicular development and atresia. One such modulator of ovarian function is the prorenin-renin-angiotensin system (PRAS) which seems to be associated with atresia. Although it is primarily under gonadotrophic control, the expression of the ovarian PRAS is also shown here to be subject to modulation by intraovarian factors. Addition of granulosa cell conditioned medium to bovine theca cells inhibited the LH-stimulated prorenin secretion in a dose-dependent manner, which leads to the assumption that granulosa cells secrete a factor(s) that, even in the presence of LH, keeps prorenin secretion low. Since growth factors and cytokines are known to be produced by granulosa cells, we have evaluated the effects of tumour necrosis factor alpha, basic fibroblast growth factor and transforming growth factor alpha on the LH- and 8Br-cAMP-induced prorenin secretion, and observed that all agonists inhibited the LH- and 8Br-cAMP-stimulated prorenin secretion in a dose-dependent manner. In contrast, addition of transforming growth factor beta, a secretory product of theca cells, further augmented gonadotrophin-induced prorenin synthesis. In conclusion, we assume that in the presence of healthy granulosa cells, suppression of the ovarian PRAS by granulosa cell derived factors may prevent a follicle from undergoing atresia, whereas in the presence of atretic granulosa cells, theca cell derived factors may enhance the expression of the PRAS, resulting in follicular atresia.