Molecular basis of BMP-15 biological activity

University Of California San Diego, La Jolla CA

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Abstract

Bone Morphogenic Protein-15 is a newly discovered member of the TGF-P superfamily which is secreted by oocytes. Recent studies from our laboratory have identified granulosa cells as a target cell type for this growth factor, and have demonstrated that in these cells, BMP-15 is capable of stimulating mitosis and inhibiting FSH receptor mRNA expression. These findings establish the novel concept that this oocyte- derived factor is involved in regulating two major aspects of follicular development: stimulating proliferation and inhibiting FSH-dependent cytodifferentiation. The goal of the present study is to elucidate the molecular mechanisms responsible for BMP-15 biological activity in granulosa cells. Specific Aim 1 Identify the cell surface receptors for BMP-15 on granulosa cells and elucidate the subsequent downstream signaling pathway. Specific Aim 2 Determine whether BMP-15 reduces FSH binding sites on the surface of granulosa cells and explore the mechanism by which BMP-15 inhibits FSH receptor gene expression.