FOLLICULAR MATURATION AND ATRESIA - POSSIBLE ROLE OF INTRAOVARIAN REGULATORY FACTORS

In addition to the gonadotrophins, factors known to be present or prod uced within the ovary are also involved in the regulation of follicula r development and atresia. One such modulator of ovarian function is t he prorenin-renin-angiotensin system (PRAS) which seems to be associat ed with atresia. Although it is primarily under gonadotrophic control, the expression of the ovarian PRAS is also shown here to be subject t o modulation by intraovarian factors. Addition of granulosa cell condi tioned medium to bovine theca cells inhibited the LH-stimulated proren in secretion in a dose-dependent manner, which leads to the assumption that granulosa cells secrete a factor(s) that, even in the presence o f LH, keeps prorenin secretion low. Since growth factors and cytokines are known to be produced by granulosa cells, we have evaluated the ef fects of tumour necrosis factor alpha, basic fibroblast growth factor and transforming growth factor a on the LH- and 8Br-cAMP-induced prore nin secretion, and observed that all agonists inhibited the LH- and 8B r-cAMP-stimulated prorenin secretion in a dose-dependent manner. In co ntrast, addition of transforming growth factor beta, a secretory produ ct of theca cells, further augmented gonadotrophin-induced prorenin sy nthesis. In conclusion, we assume that in the presence of healthy gran ulosa cells, suppression of the ovarian PRAS by granulosa cell derived factors may prevent a follicle from undergoing atresia, whereas in th e presence of atretic granulosa cells, theca cell derived factors may enhance the expression of the PRAS, resulting in follicular atresia.