Gremlin, noggin, chordin and follistatin differentially modulate BMP-induced suppression of androgen secretion by bovine ovarian theca cells
Gremlin, noggin, chordin and follistatin differentially modulate BMP-induced suppression of androgen secretion by bovine ovarian theca cells
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DOI：
10.1530/jme-18-0198
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发表时间：
2019-01-01
影响因子：
3.5
通讯作者：
Knight, Phil G.
中科院分区：
文献类型：
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作者：
Glister, Claire;Regan, Sheena L.;Knight, Phil G.
骨形态发生蛋白（BMPs）被认为是卵泡功能和类固醇生成的卵巢内调节因子，但缺乏关于卵巢中共同表达的细胞外结合蛋白调节BMP信号传导的信息。在这项研究中，我们比较了四种BMP结合蛋白（gremlin，noggin，chordin，follistatin）拮抗四种不同的BMP（BMP 2，BMP 4，BMP 6，BMP 7）对LH诱导的牛卵泡膜细胞分泌雄烯二酮的作用的能力。在此研究的四种BMP结合蛋白和BMP的表达先前已在牛卵泡中记录。所有四种BMP抑制雄烯二酮分泌> 85%。与gremlin共同治疗拮抗BMP 2-和，不太有力，BMP 4-诱导的雄激素分泌抑制，但不影响对BMP 6和BMP 7的反应。Noggin拮抗三种BMP的作用（等级顺序：BMP 4> BMP 2> BMP 7），但不影响对BMP 6的反应。卵泡抑素部分逆转BMP 6对雄激素分泌的抑制作用，但不影响BMP 2，BMP 4和BMP 7的作用。Chordin对四种BMP中的任何一种的反应都没有影响。BMP 6处理上调GREM 1、NOG、CHRD和SMAD 6 mRNA的表达，同时抑制4种BMP的表达。与以前的工作记录不同的骨形态发生蛋白，骨形态发生蛋白结合蛋白和信号受体的卵巢内表达一起，这些观察结果加强了这样的结论，即细胞外结合蛋白选择性地调节骨形态发生蛋白依赖性改变卵泡膜类固醇。因此，它们可能构成BMP的这种和其他卵巢内作用的重要调节组分。
Bone morphogenetic proteins (BMPs) are firmly implicated as intra-ovarian regulators of follicle function and steroidogenesis, but information is lacking regarding the regulation of BMP signalling by extracellular binding proteins co-expressed in the ovary. In this study, we compared the abilities of four BMP-binding proteins (gremlin, noggin, chordin, follistatin) to antagonize the action of four different BMPs (BMP2 BMP4, BMP6, BMP7) on LH-induced androstenedione secretion by bovine theca cells in primary culture. Expression of the four BMP-binding proteins and BMPs investigated here has previously been documented in bovine follicles. All four BMPs suppressed androstenedione secretion by >85%. Co-treatment with gremlin antagonized BMP2- and, less potently, BMP4-induced suppression of androgen secretion but did not affect responses to BMP6 and BMP7. Noggin antagonized the effects of three BMPs (rank order: BMP4 > BMP2 > BMP7) but did not affect the response to BMP6. Follistatin partially reversed the suppressive effects of BMP6 on androgen secretion but did not affect BMP2, BMP4 and BMP7 action. Chordin had no effect on the response to any of the four BMPs. BMP6 treatment upregulated thecal expression of GREM1, NOG, CHRD and SMAD6 mRNA whilst inhibiting expression of the four BMPs. Taken together with previous work documenting the intra-ovarian expression of different BMPs, BMP-binding proteins and signalling receptors, these observations reinforce the conclusion that extracellular binding proteins selectively modulate BMP-dependent alterations in thecal steroidogenesis. As such they likely constitute an important regulatory component of this and other intra-ovarian actions of BMPs.