Ovarian transforming growth factor-β (TGF-β) receptors: In-vitro effects of follicle stimulating hormone, epidermal growth factor and TGF-β on receptor expression in human preantral follicles

Abstract

The expression patterns of transforming growth factor (TGF)-β receptor type I (TβRI) and -II (TβRII) in preand post-menopausal human ovaries, and the in-vitro effects of follicle stimulating hormone (FSH), epidermal growth factor (EGF) and transforming growth factor-β1 (TGF-βI) on receptor expression in preantral follicles were evaluated using immunohistochemistry and immunoblotting. Both types of receptor were present in granulosa, theca and interstitial cells; however, more mural than antral granulosa cells were TβRII positive. Overall, more cells expressed TβRI than TβRII. TβRI and TβRII expressions were detected in the membrane as well as in the soluble fractions. However, marked increases in TβRII and TβRI expression in the soluble fraction and corresponding decreases in the membrane fraction were noted in the post-menopausel ovary. Preantral follicles in class I and 2 responded in vitro to FSH and EGF with increased growth and a corresponding increase in TβRII expression in granulosa cells; however, TGF-β did not infiueilce follicular growth or receptor expression. There was no apparent change in follicular TβRI immunoreactivity regardless of test factors or follicular growth status. These results suggest that TβRI and TβRII are expressed differentially in human ovarian cells, particularly in the granulosa cells. The shift in TβR-I and-II from transmembrane to soluble fraction after menopause indicates that the endocrine milieu provided by the granulosa cells positively influences receptor induction in the membrane and, hence, the biological action of TGF-β FSH- and EGF-induced preantral follicular development is associated with a selective induction of TβRII and may indicate a mechanism whereby gonadotrophins and growth factor(s) regulate preantral folliculogenesis.