Taniguchi Hiroaki, Komiyama Junichi, Viger Robert S, Okuda Kiyoshi
Department of Obstetrics and Gynecology, Centre de Recherche en Biologie de la Reproduction (CRBR), Laval University, Quebec City, Quebec, Canada.
Mol Reprod Dev. 2009 Sep;76(9):873-80. doi: 10.1002/mrd.21054.
The corpus luteum (CL) is the major site of progesterone (P4) production during the luteal phase of the estrous cycle in cattle. To better understand the molecular mechanisms underlying P4 production, we compared the mRNA and protein expression profiles of key components of the steroidogenic pathway (StAR, CYP11A, and 3beta-HSD) during the bovine CL luteal phase with that of several transcription factors (NR5A1, NR5A2, GATA4, GATA6) known for their roles in the control of steroidogenic gene expression. In the bovine CL, StAR, CYP11A, and 3beta-HSD mRNA and protein levels remained constant at the mid and late luteal phases but markedly declined at the regressed luteal stage. NR5A1 and NR5A2 exhibited a similar pattern with a significant decrease in expression at the regressed luteal stage. Both GATA4 and GATA6 mRNA and proteins could be detected in bovine CL; GATA6 levels, however, were generally higher. Although GATA4 expression did not change during the luteal phase, GATA6 showed a marked decrease at the regressed luteal stage, like NR5A1, NR5A2, and the other steroidogenic markers. Thus, we suggest that NR5A1, NR5A2, and GATA6, but not GATA4, contribute to the transcriptional regulation of steroidogenic gene expression, and hence P4 production, in the bovine CL. Furthermore, we have demonstrated the association of NR5A1 and NR5A2 with the bovine StAR promoter in the mid-luteal CL using chromatin immunoprecipitation, suggesting that these factors have definitive roles in the regulation of StAR gene transcription in vivo.
黄体（CL）是牛发情周期黄体期孕酮（P4）产生的主要部位。为了更好地理解P4产生的分子机制，我们比较了牛CL黄体期类固醇生成途径关键成分（StAR、CYP11A和3β-HSD）的mRNA和蛋白质表达谱，以及几种已知在类固醇生成基因表达调控中起作用的转录因子（NR5A1、NR5A2、GATA4、GATA6）的表达谱。在牛CL中，StAR、CYP11A和3β-HSD的mRNA和蛋白质水平在黄体中期和后期保持恒定，但在黄体退化期显著下降。NR5A1和NR5A2呈现相似模式，在黄体退化期表达显著降低。在牛CL中可检测到GATA4和GATA6的mRNA及蛋白质；然而，GATA6的水平通常更高。尽管GATA4的表达在黄体期没有变化，但GATA6在黄体退化期像NR5A1、NR5A2和其他类固醇生成标志物一样显著下降。因此，我们认为NR5A1、NR5A2和GATA6而非GATA4参与牛CL中类固醇生成基因表达的转录调控，进而参与P4的产生。此外，我们利用染色质免疫沉淀法证明了在黄体中期CL中NR5A1和NR5A2与牛StAR启动子的关联，表明这些因子在体内对StAR基因转录的调控中具有决定性作用。
