THE POTENTIAL ROLES OF INTRAOVARIAN PEPTIDES IN NORMAL AND ABNORMAL MECHANISMS OF REPRODUCTIVE PHYSIOLOGY

Normal and abnormal follicular growth and steroidogenesis depend on go nadotropins as well as intraovarian peptide and polypeptide growth fac tors, which may mediate or potentiate gonadotropin action. Epidermal g rowth factor is mitogenic to ovarian granulosa and is a potent inhibit or of granulosa aromatase. it may be involved in the apparent arrest o f follicular development commonly seen in women with polycystic ovaria n syndrome as well as in the blunted response to gonadotropins seen in this syndrome. Insulin-like growth factors are also mitogenic to ovar ian granulosa, but in contrast to epidermal growth factor, insulin-lik e growth factor-I, both alone and in synergy with gonadotropins, is a potent stimulus of aromatase and granulosa estradiol production. Insul in-like growth factor binding proteins-2 and -4, known inhibitors of i nsulin-like growth factor action, are higher in follicular fluid from atretic and polycystic ovarian syndrome follicles compared with estrog enic follicles and may be inhibitors of gonadotropin action in follicl e selection and in polycystic ovarian syndrome. Cytokines including in terleukins, tumor necrosis factor-alpha and interferon-gamma also appe ar to play a role in modulating ovarian steroidogenesis. Activins, inh ibins, and follistatin (activin-binding protein) also affect follicula r development and steroidogenesis and may play a role in dominant foll icle selection and follicular atresia.