Mullerian inhibitory substance induces growth of rat preantral ovarian follicles

Mullerian inhibitory substance (MIS), also known as anti-Mullerian hormone, is best known as the hormone that regulates the regression of the Mulleria n duct in males. In females, MIS is expressed in granulosa cells of preantr al and early antral follicles. The specific MIS type II receptor is present in granulosa and theca cells of these small, growing follicles. Because th e role of MIS in preantral follicle development is unknown, we have evaluat ed the effect of MIS on the growth, differentiation, and apoptosis of intac t preantral follicles in a serum-free culture system. In this system, treat ment with FSH induces an increase in both follicle diameter, cell number, a nd follicle cell differentiation based on increased inhibin-alpha synthesis . Of interest, treatment with MIS enhances the effect of FSH both on follic le diameter and cell number. Although treatment with activin A also enhance s FSH effects on follicle growth, treatment with transforming growth factor (TGF)-beta inhibits the FSH effects on follicle growth. Based on in situ s taining of fragmented DNA, MIS was found to have no effect on follicle cell apoptosis, unlike its proapoptotic action on Mullerian ducts. In contrast to MIS and activin, TGF-beta was a potent proapoptotic factor for preantral follicles in culture. Analysis of inhibin-alpha expression of cultured pre antral follicles further indicated that in contrast to activin, treatment w ith MIS did not enhance FSH-stimulated follicle differentiation. Thus, MIS is a unique factor that promotes preantral follicle growth but not preantra l follicle cell differentiation and apoptosis.