A comparative study on transforming growth factor-beta and activin A for preantral follicles from adult, immature, and diethylstilbestrol-primed immature mice.

Both transformation growth factor-beta (TGFbeta) and activin belong to the TGFbeta superfamily, and each receptor is structurally related. We have shown that the action of activin A on folliculogenesis is different in immature and adult mice, so it is of interest to study whether TGFbeta has such an action on follicular development. The effect of TGFbeta on folliculogenesis was studied in isolated preantral follicles from immature, adult, and diethylstilbestrol (DES)-primed immature mice and was compared with that of activin A. TGFbeta caused a significant increase in follicular diameter and estradiol and immunoreactive inhibin secretion in adult mice in a dose-related manner, but did not affect the size of preantral follicles from immature mice. Activin A, on the other hand, caused a significant increase in the size of follicles from immature mice, but did not change the size of preantral follicles from adult mice. TGFbeta enhanced the effect of FSH, whereas activin A completely blocked the action of FSH on preantral follicles from adult mice. Such a specific action of TGFbeta and activin A was age dependent because preantral follicles obtained from 28-day-old mice, compared with those from 11- and 56-day-old mice, showed an intermediate reaction to TGFbeta and activin A. DES pretreatment of 11- and 28-day-old mice caused an enhanced response to FSH, but this response was completely inhibited by TGFbeta. These results indicate that both TGFbeta and activin A have proliferative action and cytodifferentiative action on granulosa cells, but the action of each is age dependent and opposite in direction. In conclusion, although both TGFbeta and activin A belong to the same family, and each receptor is structurally related, both share a specific role in early folliculogenesis before and after puberty.