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Gene Review

Gdf9  -  growth differentiation factor 9

Rattus norvegicus

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Disease relevance of Gdf9

  • Although targeted gene disruption of GDF-9, an oocyte derived growth factor, leads to an arrest of folliculogenesis and causes infertility in female mice, little is known on the expression of GDF-9 protein in the ovary [1].
  • The objective of this study was to examine the effects of galactose on initiation of folliculogenesis in the peripubertal interval and the connection between galactose toxicity and GDF-9 expression in the ovary [2].

High impact information on Gdf9

  • This BMP-6 activity resembles BMP-15 but differs from GDF-9 activities [3].
  • In cultured rat granulosa cells from early antral follicles, treatment with GDF-9 stimulated the CAGA-luciferase reporter activity and induced the phosphorylation of Smad3 [4].
  • In conclusion, although GDF-9 binds to the BMP-activated type II receptor, its downstream actions are mediated by the type I receptor, ALK5, and the Smad2 and Smad3 proteins [4].
  • Using P19 cells, we now report that GDF-9 treatment stimulated the CAGA-luciferase reporter known to be responsive to TGF-beta mediated by the type I receptor, activin receptor-like kinase (ALK)5 [4].
  • Furthermore, transfection with small interfering RNA for ALK5 or overexpression of the inhibitory Smad7 resulted in dose-dependent suppression of GDF-9 actions [4].

Biological context of Gdf9


Anatomical context of Gdf9


Associations of Gdf9 with chemical compounds


Regulatory relationships of Gdf9


Other interactions of Gdf9

  • After overexpression of ALK5, with or without exogenous Smad3, the Cos7 cells gained GDF-9 responsiveness based on the CAGA-luciferase reporter assay [4].
  • Growth differentiation factor-9 (GDF-9) and activin A, at the same concentration as TGFbeta1 (10 ng/ml), stimulated LOX mRNA and activity within 6 h, although overall expression was higher at 48 h [13].
  • Treatment with FSH or GDF-9 resulted in increased inhibin-alpha gene promoter activity, and combined treatment with both led to synergistic increases [5].

Analytical, diagnostic and therapeutic context of Gdf9


  1. Localization of growth differentiation factor-9 (GDF-9) mRNA and protein in rat ovaries and cDNA cloning of rat GDF-9 and its novel homolog GDF-9B. Jaatinen, R., Laitinen, M.P., Vuojolainen, K., Aaltonen, J., Louhio, H., Heikinheimo, K., Lehtonen, E., Ritvos, O. Mol. Cell. Endocrinol. (1999) [Pubmed]
  2. Dietary galactose inhibits GDF-9 mediated follicular development in the rat ovary. Liu, G., Shi, F., Blas-Machado, U., Yu, R., Davis, V.L., Foster, W.G., Magoffin, D.A., Hughes, C.L. Reprod. Toxicol. (2006) [Pubmed]
  3. Biological function and cellular mechanism of bone morphogenetic protein-6 in the ovary. Otsuka, F., Moore, R.K., Shimasaki, S. J. Biol. Chem. (2001) [Pubmed]
  4. Growth differentiation factor-9 signaling is mediated by the type I receptor, activin receptor-like kinase 5. Mazerbourg, S., Klein, C., Roh, J., Kaivo-Oja, N., Mottershead, D.G., Korchynskyi, O., Ritvos, O., Hsueh, A.J. Mol. Endocrinol. (2004) [Pubmed]
  5. Growth differentiation factor-9 stimulates inhibin production and activates Smad2 in cultured rat granulosa cells. Roh, J.S., Bondestam, J., Mazerbourg, S., Kaivo-Oja, N., Groome, N., Ritvos, O., Hsueh, A.J. Endocrinology (2003) [Pubmed]
  6. Molecular cloning of porcine growth differentiation factor 9 (GDF-9) cDNA and its role in early folliculogenesis: direct ovarian injection of GDF-9 gene fragments promotes early folliculogenesis. Shimizu, T., Miyahayashi, Y., Yokoo, M., Hoshino, Y., Sasada, H., Sato, E. Reproduction (2004) [Pubmed]
  7. Adverse effects of methylphenidate on the reproductive axis of adolescent female rats. Chatterjee-Chakrabarty, S., Miller, B.T., Collins, T.J., Nagamani, M. Fertil. Steril. (2005) [Pubmed]
  8. Recombinant growth differentiation factor-9 (GDF-9) enhances growth and differentiation of cultured early ovarian follicles. Hayashi, M., McGee, E.A., Min, G., Klein, C., Rose, U.M., van Duin, M., Hsueh, A.J. Endocrinology (1999) [Pubmed]
  9. Bone morphogenetic protein 15 and growth differentiation factor 9 co-operate to regulate granulosa cell function. McNatty, K.P., Juengel, J.L., Reader, K.L., Lun, S., Myllymaa, S., Lawrence, S.B., Western, A., Meerasahib, M.F., Mottershead, D.G., Groome, N.P., Ritvos, O., Laitinen, M.P. Reproduction (2005) [Pubmed]
  10. Expression of growth differentiation factor-9 messenger ribonucleic acid in ovarian and nonovarian rodent and human tissues. Fitzpatrick, S.L., Sindoni, D.M., Shughrue, P.J., Lane, M.V., Merchenthaler, I.J., Frail, D.E. Endocrinology (1998) [Pubmed]
  11. Growth differentiation factor-9 stimulates rat theca-interstitial cell androgen biosynthesis. Solovyeva, E.V., Hayashi, M., Margi, K., Barkats, C., Klein, C., Amsterdam, A., Hsueh, A.J., Tsafriri, A. Biol. Reprod. (2000) [Pubmed]
  12. Growth differentiation factor-9 stimulates proliferation but suppresses the follicle-stimulating hormone-induced differentiation of cultured granulosa cells from small antral and preovulatory rat follicles. Vitt, U.A., Hayashi, M., Klein, C., Hsueh, A.J. Biol. Reprod. (2000) [Pubmed]
  13. Lysyl oxidase gene expression and enzyme activity in the rat ovary: regulation by follicle-stimulating hormone, androgen, and transforming growth factor-beta superfamily members in vitro. Harlow, C.R., Rae, M., Davidson, L., Trackman, P.C., Hillier, S.G. Endocrinology (2003) [Pubmed]
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