Growth differentiation factor-9
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
- ^ 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.
- ^ a b "Entrez Gene: GDF9 growth differentiation factor 9". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2661.
- ^ 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.
- ^ 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
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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. PMC 14828. PMID 10712517. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=14828.
- 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
- 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928.
- 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1356129.
- 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
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| TGF beta superfamily of ligands |
TGF beta family (TGF-β1, TGF-β2, TGF-β3)
Bone morphogenetic proteins (BMP2, BMP3, BMP4, BMP5, BMP6, BMP7, BMP8a, BMP8b, BMP10 , BMP15)
Growth differentiation factors (GDF1, GDF2, GDF3, GDF5, GDF6, GDF7, Myostatin/GDF8, GDF9, GDF10, GDF11, GDF15)
Other ( Activin and inhibin, Anti-müllerian hormone, Nodal)
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TGF beta receptors
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B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)
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