Growth differentiation factor-9 signaling in the ovary

Growth differentiation factor-9 (GDF-9) is an oocyte-derived growth factor and a member of the transforming growth factor-beta (TGF-beta) superfamily. In GDF-9 null mice, follicle development is arrested at the primary stage and in vivo treatment with GDF-9 enhances the progression of primordial and primary follicles into small preantral follicles. In vitro, GDF-9 promotes granulosa cell proliferation but inhibits FSH-induced differentiation. GDF-9 also promotes the differentiation of theca cells in vivo and in vitro. GDF-9, like TGF-beta or activin, is a close member of the bone morphogenetic proteins (BMPs) family. GDF-9 likely initiates signaling by assembling two related but distinct types of receptors, both of which are serine/threonine kinases with a single transmembrane domain. The ligand-receptor binding activates intracellular transcription factors called Smads. In granulosa cells, Vitt et al. have shown that the BMP receptor type II is involved in GDF-9 signaling. The type I receptors and the Smad pathway for GDF-9 remain to be identified.