Bone morphogenetic protein 6 promotes FSH receptor and anti-Mullerian hormone mRNA expression in granulosa cells from hen prehierarchal follicles
Bone morphogenetic protein 6 promotes FSH receptor and anti-Mullerian hormone mRNA expression in granulosa cells from hen prehierarchal follicles
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DOI：
10.1530/rep-11-0271
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发表时间：
2012-06-01
期刊：
影响因子：
3.8
通讯作者：
Johnson, A. L.
中科院分区：
文献类型：
--
作者：
Ocon-Grove, O. M.;Poole, D. H.;Johnson, A. L.
越来越多的文献表明，骨形态发生蛋白(BMPs)在调节卵泡发育的不同阶段发挥着重要作用。Bmp6的几种作用以前已经在母鸡的卵巢中报道过，但仅在选择后(排卵前)的卵泡中。最初的假设是Bmp6增加了FSH受体(FSHR)在6-8 mm级卵泡(6-8GC)颗粒层的表达。Bmp6mRNA在未分化(1-8 mm)卵泡中的表达水平高于精选(>；=9 mm)卵泡。重组人(Rh)Bmp6在6-8GC中启动Smad1、5、8信号转导，并以剂量相关方式促进FSHR基因的表达。此外，用rhBMP6预培养21h，然后用FSH刺激3h，可增加cAMP积累、STAR(STAR)表达和孕酮产生。有趣的是，重组人骨形态发生蛋白6还增加了6-8胃癌细胞中抗苗勒氏激素(AMH)的表达。这个相关的BMP家族成员此前被认为在卵泡发育过程中负向调节FSH的反应性。考虑到这些数据，我们认为Bmp6在层级前卵泡中的旁分泌和/或自分泌作用之一是维持FSHR和AMH的mRNA表达。我们预测，在卵泡选择之前，AMH在6-8 mm卵泡的颗粒细胞内的作用之一是帮助抑制FSHR信号，防止颗粒细胞过早分化。在选择时，我们推测直接负责选择的尚未确定的信号启动了FSH反应。结果，FSH信号抑制了AMH的表达，并启动了所选卵泡内颗粒的分化。再生产(2012)143 825-833
A growing body of literature provides evidence of a prominent role for bone morphogenetic proteins (BMPs) in regulating various stages of ovarian follicle development. Several actions for BMP6 have been previously reported in the hen ovary, yet only within postselection (preovulatory) follicles. The initial hypothesis tested herein is that BMP6 increases FSH receptor (FSHR) mRNA expression within the granulosa layer of prehierarchal (6-8 mm) follicles (6-8 GC). BMP6 mRNA is expressed at higher levels within undifferentiated (1-8 mm) follicles compared with selected (>= 9 mm) follicles. Recombinant human (rh) BMP6 initiates SMAD1, 5, 8 signaling in cultured 6-8 GC and promotes FSHR mRNA expression in a dose-related fashion. In addition, a 21 h preculture with rhBMP6 followed by a 3 h challenge with FSH increases cAMP accumulation, STAR (StAR) expression, and progesterone production. Interestingly, rhBMP6 also increases expression of anti-Mullerian hormone (AMH) mRNA in cultured 6-8 GC. This related BMP family member has previously been implicated in negatively regulating FSH responsiveness during follicle development. Considering these data, we propose that among the paracrine and/or autocrine actions of BMP6 within prehierarchal follicles is the maintenance of both FSHR and AMH mRNA expression. We predict that before follicle selection, one action of AMH within granulosa cells from 6 to 8 mm follicles is to help suppress FSHR signaling and prevent premature granulosa cell differentiation. At the time of selection, we speculate that the yet undefined signal directly responsible for selection initiates FSH responsiveness. As a result, FSH signaling suppresses AMH expression and initiates the differentiation of granulosa within the selected follicle. Reproduction (2012) 143 825-833