None the less, despite treating follicles relatively late in the follicle wave we still demonstrated an inhibitory effect on follicle growth and oestradiol production through blocking the activation of Akt and Erk pathways. The significant decrease in oestradiol concentrations in follicles treated in vivo with Akt and Erk inhibitors agrees with the results from Experiments 1 and 2 where inhibi tion of the Erk pathway inhibited FSH induced oestradiol production and inhibition of the Akt pathways inhibited both FSH and IGF induced oestradiol production in granulosa cells in vitro. Androstenedione secre tion in cultured theca cells was also abrogated by inhibi tion of both the Akt and Erk pathways.
In Experiment 3, the inhibitors were injected directly into the antral cavity and it is reasonable to suggest that gran ulosa cells would be first to be exposed to and affected by the inhibitors. However, it is possible that the inhibitors might have diffused through the granulosa layer of cells selleck chemicals into the theca layer and affect signalling pathways there. Thus the significant reductions in follicular fluid oestra diol concentrations may be due to the effect of the Akt and Erk inhibitors on both granulosa and theca cells in com bination. In summary, this study demonstrates a role for the Akt and Erk pathways in mediating the actions of FSH and IGF on granulosa cells and LH on theca cells in vitro and their role in follicle growth and oestradiol secretion in vivo.
While both pathways appear to be important for the actions of these hormones in both cell types, we conclude that the actions of the Akt pathway are more pronounced than the Erk pathway in granulosa cells and vice versa in the in theca cells. None the less, administration BRD-9424 cancer of inhibi tors of these pathways in vivo inhibited follicle growth and reduced follicular fluid oestradiol concentrations. We sug gest that the successful functioning of healthy follicles requires the activation of the Akt and Erk signal transduc tion pathways, and that these pathways are necessary for ovarian follicle growth and development. Background The principal function of ovarian theca cells is steroid hor mone production. Theca cells play an important role in controlling ovarian steroidogenesis by providing aroma tizable androgens for granulosa cell estrogen biosynthesis.
Androgens also function as local regulators of ovarian folliculogenesis upon binding androgen receptors local ized to granulosa cells, stromal cells, and oocytes. Androgen receptor null mice culminate in reduced fertility and premature ovarian failure, indicating that andro gens are necessary for reproductive function and fertility. Normal ovarian function requires accurate regulation of steroidogenic activity of theca cells through extraovarian and intraovarian mechanisms.