The cooperative effect of growth and differentiation factor-9 and bone morphogenetic protein (BMP)-15 on granulosa cell function is modulated primarily through BMP receptor II

The cooperative effect of growth and differentiation factor-9 and bone morphogenetic protein (BMP)-15 on granulosa cell function is modulated primarily through BMP receptor II
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DOI:
10.1210/en.2007-1328
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发表时间:
2008-03-01
期刊:
影响因子:
4.8
通讯作者:
Juengel, Jennifer L.
Juengel, Jennifer L.
中科院分区:
医学2区
文献类型:
--
作者:
Edwards, Sara J.;Reader, Karen L.;Juengel, Jennifer L.

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生长和分化因子9(GDF 9)和骨形态发生蛋白15(BMP 15,GDF 9 B)是卵母细胞衍生的蛋白质,对卵泡的生长和功能至关重要。此外,绵羊(o)GDF 9和oBW 15协同增加H-3-胸苷掺入和α-腺苷二酸产生,并抑制大鼠或绵羊颗粒细胞的孕酮产生。尽管已经确定了这些蛋白质单独作用的受体,但参与介导GDF 9和BMP 15的协同作用的受体是未知的。在这项研究中,研究了I型和II型TGF β受体的胞外结构域对由oGDF 9和oBMP 15刺激的大鼠颗粒细胞的H-3-胸苷掺入的影响。H-3-胸苷掺入的刺激被BMP受体II(BMPRII)胞外结构域完全阻断,但不受任何其他II型或I型受体的影响。这些结果表明oGDF 9和oBMIP 15的初始相互作用是与BMPRII的,并且I型受体被募集或已经与BMPRII相关联以介导这些生长因子的协同作用。
Growth and differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15, GDF9B) are oocyte-derived proteins essential for the growth and function of ovarian follicles. Moreover, ovine (o) GDF9 and oBW15 cooperate to increase both H-3-thymidine incorporation and a-inhibin production and to inhibit progesterone production by rat or ovine granulosa cells. Although the receptors through which these proteins act individually have been determined, the receptor(s) involved in mediating the cooperative effects of GDF9 and BMP15 is (are) unknown. In this study, the effects of the extracellular domains of the types I and II TGF beta receptors on H-3-thymidine incorporation by rat granulosa cells stimulated by oGDF9 and oBMP15 were investigated. Stimulation of H-3-thymidine incorporation was completely blocked by the BMP receptor II (BMPRII) extracellular domain but unaffected by any other type II or any type I receptor. These results suggest that the initial interaction of oGDF9 and oBMIP15 is with BMPRII and that a type I receptor is either recruited or already associated with BMPRII to mediate the cooperative effects of these growth factors.