Abstract
The expression patterns of transforming growth factor (TGF)-beta receptor type I (TbetaRI) and -II (TbetaRII) in pre- and post-menopausal human ovaries, and the in-vitro effects of follicle stimulating hormone (FSH), epidermal growth factor (EGF) and transforming growth factor-beta1 (TGF-beta1) 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 TbetaRII positive. Overall, more cells expressed TbetaRI than TbetaRII. TbetaRI and TbetaRII expressions were detected in the membrane as well as in the soluble fractions. However, marked increases in TbetaRII and TbetaRI expression in the soluble fraction and corresponding decreases in the membrane fraction were noted in the post-menopausal ovary. Preantral follicles in class 1 and 2 responded in vitro to FSH and EGF with increased growth and a corresponding increase in TbetaRII expression in granulosa cells; however, TGF-beta did not influence follicular growth or receptor expression. There was no apparent change in follicular TbetaRI immunoreactivity regardless of test factors or follicular growth status. These results suggest that TbetaRI and TbetaRII are expressed differentially in human ovarian cells, particularly in the granulosa cells. The shift in TbetaR-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-beta. FSH- and EGF-induced preantral follicular development is associated with a selective induction of TbetaRII and may indicate a mechanism whereby gonadotrophins and growth factor(s) regulate preantral folliculogenesis.
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