Bone Morphogenetic Protein-15 IDENTIFICATION OF TARGET CELLS AND BIOLOGICAL FUNCTIONS

作者: Fumio Otsuka , Zuxu Yao , Taek-hoo Lee , Shin Yamamoto , Gregory F. Erickson

DOI: 10.1074/JBC.M007428200

关键词: Growth factorCell biologyCell growthGrowth differentiation factor-9OocyteBone morphogenetic protein 7Internal medicineBone morphogenetic protein 15HormoneFolliculogenesisEndocrinologyBiology

摘要: In developing ovarian follicles, the regulation of cell proliferation and differentiation is tightly coordinated. Precisely how this coordination achieved unknown, but recent observations have suggested that molecules emitted by oocyte are involved in process. The newly discovered oocyte-specific growth factor, bone morphogenetic protein-15 (BMP-15), one such molecule. At present, nothing known about target cells biological functions BMP-15. To fill gap our knowledge, recombinant BMP-15 its antibody were produced used to determine expression bioactivity. mRNA protein shown be co-expressed oocytes throughout folliculogenesis, supporting idea a physiological regulator follicle and/or differentiation. test this, we primary cultures rat granulosa (GCs). We found potent stimulator GC proliferation, importantly, mitogenic effect was follicle-stimulating hormone (FSH)-independent. By contrast, alone had no on steroidogenesis. However, it marked decrease FSH-induced progesterone production, FSH-stimulated estradiol production. This result indicates selective modulator FSH action. summary, study identifies GCs as first for Moreover, stimulation differential two crucial steroid hormones Significantly, factor can coordinate way reflects normal physiology.

参考文章(26)
Susan M. Galloway, Kenneth P. McNatty, Lisa M. Cambridge, Mika P.E. Laitinen, Jennifer L. Juengel, T. Sakari Jokiranta, Robert J. McLaren, Kaisu Luiro, Ken G. Dodds, Grant W. Montgomery, Anne E. Beattie, George H. Davis, Olli Ritvos, Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner. Nature Genetics. ,vol. 25, pp. 279- 283 ,(2000) , 10.1038/77033
Chesnel F, Eppig Jj, Wigglesworth K, O'Brien Mj, Pendola Fl, Hirao Y, Watanabe S, Oocyte control of granulosa cell development: how and why. Human Reproduction. ,vol. 12, pp. 127- 132 ,(1997)
Jennifer L. Dube, Pei Wang, Julia Elvin, Karen M. Lyons, Anthony J. Celeste, Martin M. Matzuk, The Bone Morphogenetic Protein 15 Gene Is X-Linked and Expressed in Oocytes Molecular Endocrinology. ,vol. 12, pp. 1809- 1817 ,(1998) , 10.1210/MEND.12.12.0206
Risto Jaatinen, Mika P Laitinen, Kaisa Vuojolainen, Johanna Aaltonen, Henna Louhio, Kristiina Heikinheimo, Eero Lehtonen, Olli Ritvos, 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 Molecular and Cellular Endocrinology. ,vol. 156, pp. 189- 193 ,(1999) , 10.1016/S0303-7207(99)00100-8
Laura A. Hutchinson, Jock K. Findlay, Fiona L. de Vos, David M. Robertson, Effects of bovine inhibin, transforming growth factor-β and bovine activin-A on granulosa cell differentiation Biochemical and Biophysical Research Communications. ,vol. 146, pp. 1405- 1412 ,(1987) , 10.1016/0006-291X(87)90806-0
Shao-Yao Ying, Ann Becker, Nicholas Ling, Naoto Ueno, Roger Guillemin, Inhibin and beta type transforming growth factor (TGFβ) have opposite modulating effects on the follicle stimulating hormone (FSH)-induced aromatase activity of cultured rat granulosa cells Biochemical and Biophysical Research Communications. ,vol. 136, pp. 969- 975 ,(1986) , 10.1016/0006-291X(86)90427-4
Eli Y. Adashi, Carol E. Resnick, Eleuterio R. Hernandez, Jeffrey V. May, A.F. Purchio, Daniel R. Twardzik, Ovarian transforming growth factor-β (TGFβ): cellular site(s), and mechanism(s) of action Molecular and Cellular Endocrinology. ,vol. 61, pp. 247- 256 ,(1989) , 10.1016/0303-7207(89)90136-6
Michael Wigler, Angel Pellicer, Saul Silverstein, Richard Axel, Biochemical transfer of single-copy eucaryotic genes using total cellular DNA as donor Cell. ,vol. 14, pp. 725- 731 ,(1978) , 10.1016/0092-8674(78)90254-4
Jinwen Dong, David F. Albertini, Katsuhiko Nishimori, T. Rajendra Kumar, Naifang Lu, Martin M. Matzuk, Growth differentiation factor-9 is required during early ovarian folliculogenesis Nature. ,vol. 383, pp. 531- 535 ,(1996) , 10.1038/383531A0