|Growth Inhibition Induced by GDF‑9 and Neutralization by Mouse GDF‑9 Antibody. Recombinant Mouse GDF‑9 (Catalog # 739-G9) induces growth inhibition in the Mv1Lu mink lung epithelial cell line in the presence of in a dose-dependent manner (orange line), as measured by Resazurin (Catalog # AR002). Growth Inhibition elicited by Recombinant Mouse GDF‑9 (0.5 µg/mL) is neutralized (green line) by increasing concentrations of Rat Anti-Mouse GDF‑9 Monoclonal Antibody (Catalog # MAB739). The ND50 is typically 0.4-2.4 µg/mL.|
Growth differentiation factor-9 (GDF-9) is a member of the transforming growth factor-beta (TGF-beta ) superfamily, and is an oocyte secreted paracrine factor essential for mammalian ovarian folliculogenesis (1‑2). Mouse GDF-9 is synthesized as a 441 amino acid (aa) prepropeptide that contains a 29 aa signal sequence, a 277 aa propeptide, and a 135 aa mature chain. Residues 340‑441 constitute a TGF-beta like domain. In addition, there is one potential site of N-linked glycosylation in the mature chain. Unlike other members of the TGF-beta superfamily, GDF-9 lacks the conserved cysteine residue that is believed to form the sole disulfide linkage between subunits in other family members (3). Mature mouse GDF-9 shares 90% aa sequence identity with mature human GDF 9. The protein is expressed throughout the development of the maturing follicle (2). GDF-9 functions as a paracrine factor in the regulation of granulosa cell proliferation and differentiation, and is essential for fertility (2, 4). Studies on GDF-9 null mice have demonstrated arrested follicular development at the primary follicle stage (5). Mouse GDF-9 induces Smad2 phosphorylation and inhibin production in rat diethylstilbestrol treated granulosa cells (6) and in human granulosa-luteal cells (7). The downstream signaling actions of GDF 9 are mediated by the type I receptor, activin receptor-like kinase 5 (ALK5), initiating the subsequent activation of Smad2 and Smad3 (2, 8). GDF 9 uses the BMP type II receptor (BMPRII) as its other signaling receptor (2, 9).