Biology of Reproduction, Vol 57, 684-688, Copyright © 1997 by Society for the Study of Reproduction

ARTICLES

Interactions between follicle-stimulating hormone and growth factors in regulation of deoxyribonucleic acid synthesis in bovine granulosa cells

F Khamsi and DT Armstrong
Toronto Fertility Sterility Institute, Ontario, Canada.

Follicle growth is regulated by the combined actions and interactions of pituitary gonadotropic hormones and local intraovarian paracrine and/or autocrine agents, including the peptide growth factors, insulin- like growth factor-I (IGF-I), and epidermal growth factor (EGF). The present study was undertaken to determine a) whether the previously demonstrated inhibitory effect of FSH on DNA synthesis was related to its ability to cause cumulus mucification as a differentiated response incompatible with continued proliferation, and b) whether increased IGF- binding proteins (IGFBP) secreted in response to FSH competed with IGF receptors, thereby inhibiting response to exogenous IGF-I. To determine the effects of cumulus mucification in modulating the mitogenic response to IGF-I, two other agents that induce cumulus mucification by different mechanisms, EGF and dibutyryl cAMP (dbcAMP), were compared with FSH. To determine the possible role of IGFBP in modulating the mitogenic response to IGF-I, an IGF-I analogue that does not bind to IGFBP, long arg3-IGF-I (LR3-IGF-I), was compared with native IGF-I for efficacy in stimulating DNA synthesis in the absence and presence of each of the above agonists. Both IGF-I and LR3-IGF-I stimulated [3H]thymidine incorporation in cumulus cells to a much greater extent than in mural granulosa cells. Incorporation in mural cells was increased by each of FSH, EGF, and dbcAMP acting by itself, and in most instances was considerably enhanced by the combined action of these agents with each of the IGF-I forms. In contrast, the considerably greater stimulatory effect of both IGF-I and LR3-IGF-I on cumulus cells was markedly decreased by each of FSH, EGF, and dbcAMP. These findings suggest that the inhibition of IGF-I-stimulated DNA synthesis in cumulus cells is a consequence of induction of cumulus cell differentiation (mucification) by FSH and EGF rather than through competition between IGF-I receptor and IGFBP secretion induced by these agents.

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