Growth differentiation factor-9

Growth differentiation factor 9
Identifiers
Symbol	GDF9
External IDs	OMIM: 601918 MGI: 95692 HomoloGene: 3851 GeneCards: GDF9 Gene
Gene ontology Molecular function • cytokine activity • transforming growth factor beta receptor binding • growth factor activity Cellular component • extracellular space • cytoplasm Biological process • oocyte growth • transforming growth factor beta receptor signaling pathway • female gamete generation • positive regulation of cell proliferation • positive regulation of pathway-restricted SMAD protein phosphorylation • negative regulation of cell growth • BMP signaling pathway • regulation of apoptotic process • regulation of MAPK cascade • cell development • SMAD protein signal transduction • regulation of progesterone secretion Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2661	14566
Ensembl	ENSG00000164404	ENSMUSG00000018238
UniProt	O60383	Q07105
RefSeq (mRNA)	NM_001288824	NM_008110
RefSeq (protein)	NP_001275753	NP_032136
Location (UCSC)	Chr 5: 132.86 – 132.87 Mb	Chr 11: 53.43 – 53.44 Mb
PubMed search

Growth/differentiation factor 9 is a protein that in humans is encoded by the GDF9 gene.^[1][2]

Growth factors synthesized by ovarian somatic cells directly affect oocyte growth and function. Growth differentiation factor-9 (GDF9) is expressed in oocytes and is thought to be required for ovarian folliculogenesis. GDF9 is a member of the transforming growth factor-beta (TGFβ) superfamily.^[2]

GDF9 plays an important role in the development of primary follicles in the ovary.^[3] It has a critical role in granulosa cell and theca cell growth, as well as in differentiation and maturation of the oocyte.^[4][5]

GDF9 has been connected to differences in ovulation rate^[6][7] and in premature cessation of ovary function,^[8] therefore has a significant role in fertility.

The cell surface receptor through which GDF9 generates a signal is the bone morphogenetic protein type II receptor (BMPR2).^[9][10]

References

1. McGrath SA, Esquela AF, Lee SJ (Jun 1995). "Oocyte-specific expression of growth/differentiation factor-9". Mol Endocrinol 9 (1): 131–6. doi:10.1210/me.9.1.131. PMID 7760846.
2. "Entrez Gene: GDF9 growth differentiation factor 9".
3. Juengel J, Bodensteiner K, Heath D, Hudson N, Moeller C, Smith P, Galloway S, Davis G, Sawyer H, McNatty K (2004). "Physiology of GDF9 and BMP15 signalling molecules". Anim Reprod Sci. 82-83: 447–60. doi:10.1016/j.anireprosci.2004.04.021. PMID 15271472.
4. Hreinsson J, Scott J, Rasmussen C, Swahn M, Hsueh A, Hovatta O (2002). "Growth differentiation factor-9 promotes the growth, development, and survival of human ovarian follicles in organ culture". J Clin Endocrinol Metab 87 (1): 316–21. doi:10.1210/jc.87.1.316. PMID 11788667. link
5. Su Y, Wu X, O'Brien M, Pendola F, Denegre J, Matzuk M, Eppig J (2004). "Synergistic roles of BMP15 and GDF9 in the development and function of the oocyte-cumulus cell complex in mice: genetic evidence for an oocyte-granulosa cell regulatory loop". Dev Biol 276 (1): 64–73. doi:10.1016/j.ydbio.2004.08.020. PMID 15531364.
6. McNatty K, Hudson N, Whiting L, Reader K, Lun S, Western A, Heath D, Smith P, Moore L, Juengel J (2007). "The Effects of Immunizing Sheep with Different BMP15 or GDF9 Peptide Sequences on Ovarian Follicular Activity and Ovulation Rate". Biol Reprod 76 (4): 552–60. doi:10.1095/biolreprod.106.054361. PMID 17093201.
7. Juengel J, Hudson N, Whiting L, McNatty K (2004). "Effects of immunization against bone morphogenetic protein 15 and growth differentiation factor 9 on ovulation rate, fertilization, and pregnancy in ewes". Biol Reprod 70 (3): 557–61. doi:10.1095/biolreprod.103.023333. PMID 14585806.
8. Kovanci E, Rohozinski J, Simpson J, Heard M, Bishop C, Carson S (2007). "Growth differentiating factor-9 mutations may be associated with premature ovarian failure". Fertil Steril 87 (1): 143–6. doi:10.1016/j.fertnstert.2006.05.079. PMID 17156781.
9. Mazerbourg S, Hsueh A (2006). "Genomic analyses facilitate identification of receptors and signalling pathways for growth differentiation factor 9 and related orphan bone morphogenetic protein/growth differentiation factor ligands". Hum Reprod Update 12 (4): 373–83. doi:10.1093/humupd/dml014. PMID 16603567.
10. Vitt U, Mazerbourg S, Klein C, Hsueh A (2002). "Bone morphogenetic protein receptor type II is a receptor for growth differentiation factor-9". Biol Reprod 67 (2): 473–80. doi:10.1095/biolreprod67.2.473. PMID 12135884.

Further reading

• McPherron AC, Lee SJ (1993). "GDF-3 and GDF-9: two new members of the transforming growth factor-beta superfamily containing a novel pattern of cysteines.". J. Biol. Chem. 268 (5): 3444–9. PMID 8429021.
• Dong J, Albertini DF, Nishimori K, et al. (1996). "Growth differentiation factor-9 is required during early ovarian folliculogenesis.". Nature 383 (6600): 531–5. doi:10.1038/383531a0. PMID 8849725.
• Aaltonen J, Laitinen MP, Vuojolainen K, et al. (1999). "Human growth differentiation factor 9 (GDF-9) and its novel homolog GDF-9B are expressed in oocytes during early folliculogenesis.". J. Clin. Endocrinol. Metab. 84 (8): 2744–50. doi:10.1210/jc.84.8.2744. PMID 10443672.
• Gilboa L, Nohe A, Geissendörfer T, et al. (2000). "Bone morphogenetic protein receptor complexes on the surface of live cells: a new oligomerization mode for serine/threonine kinase receptors.". Mol. Biol. Cell 11 (3): 1023–35. doi:10.1091/mbc.11.3.1023. PMC 14828. PMID 10712517.
• Vitt UA, Mazerbourg S, Klein C, Hsueh AJ (2003). "Bone morphogenetic protein receptor type II is a receptor for growth differentiation factor-9.". Biol. Reprod. 67 (2): 473–80. doi:10.1095/biolreprod67.2.473. PMID 12135884.
• Liao WX, Moore RK, Otsuka F, Shimasaki S (2003). "Effect of intracellular interactions on the processing and secretion of bone morphogenetic protein-15 (BMP-15) and growth and differentiation factor-9. Implication of the aberrant ovarian phenotype of BMP-15 mutant sheep.". J. Biol. Chem. 278 (6): 3713–9. doi:10.1074/jbc.M210598200. PMID 12446716.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Liao WX, Moore RK, Shimasaki S (2004). "Functional and molecular characterization of naturally occurring mutations in the oocyte-secreted factors bone morphogenetic protein-15 and growth and differentiation factor-9.". J. Biol. Chem. 279 (17): 17391–6. doi:10.1074/jbc.M401050200. PMID 14970198.
• Schmutz J, Martin J, Terry A, et al. (2004). "The DNA sequence and comparative analysis of human chromosome 5.". Nature 431 (7006): 268–74. doi:10.1038/nature02919. PMID 15372022.
• Goehler H, Lalowski M, Stelzl U, et al. (2004). "A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington's disease.". Mol. Cell 15 (6): 853–65. doi:10.1016/j.molcel.2004.09.016. PMID 15383276.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Stelzl U, Worm U, Lalowski M, et al. (2005). "A human protein-protein interaction network: a resource for annotating the proteome.". Cell 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. PMID 16169070.
• Dixit H, Rao LK, Padmalatha V, et al. (2007). "Mutational screening of the coding region of growth differentiation factor 9 gene in Indian women with ovarian failure.". Menopause (New York, N.Y.) 12 (6): 749–54. doi:10.1097/01.gme.0000184424.96437.7a. PMID 16278619.
• Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
• Laissue P, Christin-Maitre S, Touraine P, et al. (2006). "Mutations and sequence variants in GDF9 and BMP15 in patients with premature ovarian failure.". Eur. J. Endocrinol. 154 (5): 739–44. doi:10.1530/eje.1.02135. PMID 16645022.
• Palmer JS, Zhao ZZ, Hoekstra C, et al. (2007). "Novel variants in growth differentiation factor 9 in mothers of dizygotic twins.". J. Clin. Endocrinol. Metab. 91 (11): 4713–6. doi:10.1210/jc.2006-0970. PMID 16954162.
• Chand AL, Ponnampalam AP, Harris SE, et al. (2006). "Mutational analysis of BMP15 and GDF9 as candidate genes for premature ovarian failure.". Fertil. Steril. 86 (4): 1009–12. doi:10.1016/j.fertnstert.2006.02.107. PMID 17027369.
• Kovanci E, Rohozinski J, Simpson JL, et al. (2007). "Growth differentiating factor-9 mutations may be associated with premature ovarian failure.". Fertil. Steril. 87 (1): 143–6. doi:10.1016/j.fertnstert.2006.05.079. PMID 17156781.
• Hanavadi S, Martin TA, Watkins G, et al. (2007). "The role of growth differentiation factor-9 (GDF-9) and its analog, GDF-9b/BMP-15, in human breast cancer.". Ann. Surg. Oncol. 14 (7): 2159–66. doi:10.1245/s10434-007-9397-5. PMID 17453295.

External links

• growth differentiation factor 9 at the US National Library of Medicine Medical Subject Headings (MeSH)