GROWTH FACTORS IN FOLLICULAR DEVELOPMENT

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DESCRIPTION: (adapted from the applicants abstract) The use of isolated intact follicles in long term culture provides an alternative to culture of isolated cellular components of follicles. This method allows for the study of proliferating cells in their more natural follicular environment. These follicles synthesize cAMP and steroids, proliferate and respond to gonadotropins as well as express gonadotropin receptors and unique proteins. In addition, this model shows that the mitogenic action of FSH is mediated via the action of epidermal growth factor (EGF). The research plan during the past 4 years and in the proposed future grant focuses on preantral follicles about which little is known in comparison to antral follicles. The investigator has established that hamster follicular cells express EGF, transforming growth factors beta (TGF-beta1 and -beta2), EGF and TGF-beta receptors. The goal of the present proposal is to define the role(s) of hormones and growth factors in modulating the expression of EGF and TGF-beta receptors, and the functional implications of growth factor receptor expression during follicular development as a mechanism regulating folliculogenesis. The working hypothesis is that one of the mechanisms of growth factor regulated follicular development involves a negative interaction of EGF-R and TbetaR, the expressions of which act as a pivotal determinant to direct follicular cells either to proliferation or to functional differentiation (e.g., onset of androgen and estrogen synthesis)--two most fundamental requirements for follicular development. Growth factor receptor expressions in follicular cells, in turn, is critically regulated by gonadotropins, ovarian steroids and growth factors themselves. The hypothesis will be tested on preantral and antral follicles exposed to endogenous hormones in cyclic hamsters, on preantral follicles deprived of hormonal support in long term hypophysectomized (HX) hamsters, and on preantral follicles from cyclic and HX hamsters cultured in vitro in the presence of gonadotropins, ovarian steroids, EGF and TGF-beta using: (1) immunohistochemical and biochemical analyses of follicular cell proliferation, and growth factor receptor expression, (2) analysis of follicular steroidogenesis, and (3) quantitative RT-PCR analyses of TGF-beta receptor gene transcripts. The information will shed light on the mechanisms involved in hormonal control of folliculogenesis via intraovarian growth factors.