Hormone and prostaglandin F2α regulation of messenger ribonucleic acid encoding steroidogenic acute regulatory protein in human corpora lutea
Hormone and prostaglandin F2α regulation of messenger ribonucleic acid encoding steroidogenic acute regulatory protein in human corpora lutea
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DOI：
10.1385/endo:8:2:153
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发表时间：
1998-04-01
期刊：
影响因子：
3.7
通讯作者：
McLean, MP
中科院分区：
文献类型：
--
作者：
Chung, PH;Sandhoff, TW;McLean, MP
类固醇合成急性调节蛋白(STAR)通过促进胆固醇向线粒体内膜的转运，促进类固醇激素生物合成的快速增加。虽然我们的实验室最近报道了大鼠卵巢中STAR mRNA的激素调节，但在人类黄体中同样的调节需要分析。为此，利用逆转录-聚合酶链式反应(RT-PCR)技术，从人黄体RNA中扩增出858bp的人类STAR互补DNA(CDNAs)探针。通过双脱氧链末端序列分析证实了该STAR序列。用STAR cDNA探针对人黄体mRNA进行Northern杂交分析表明，该探针与一个1.6kb的主要转录本和一个4.4kb的次要转录本杂交。对不同黄体期黄体的观察表明，1.6kb转录本在黄体早期(15-19天)的基础表达显著高于黄体中期(20-23天)和黄体晚期(24-28天)。为了研究STAR mRNA的激素调节，在体外用不同浓度的人绒毛膜促性腺激素(HCG)或前列腺素F2α(PGF2α)处理黄体。HCG刺激后，1.6kb和4.4kb的STAR转录均增加。当HGC浓度分别为50和100mIU/mL时，1.6kb的转录本分别显著增加了2.2倍和1.8倍。这一增加伴随着中位孕酮水平的显著上升，相反，PCF2α处理在500和5000 ng/mL浓度下显著降低了星形信使核糖核酸(MRNA)的表达和中位孕酮水平。本研究表明，STAR基因在人黄体中受促性激素和前列腺素的调节。STAR mRNA的平行变化与孕激素水平的变化进一步支持了STAR在类固醇生成调节中的假定作用。
Steroidogenic acute regulatory (StAR) protein mediates the rapid increase in steroid hormone biosynthesis in response to tropic hormones by facilitating transport of cholesterol into the inner mitochondrial membrane. Although our laboratory has recently reported on the hormonal regulation of StAR mRNA in the rat ovary, the same regulation in the human corpus luteum requires analysis. To this end, a human StAR complementary DNA (cDNA) probe of 858 bp was generated using reverse transcriptase-PCR and RNA from human corpora lutea. The StAR sequence was confirmed by dideoxy chain-termination sequence analysis. Northern blot analysis using the StAR cDNA probe on human corpora lutea mRNA showed that the probe hybridized to a major 1.6-kb transcript and a minor 4.4-kb transcript. Examination of corpora lutea of different luteal phases revealed that the basal expression of the 1.6-kb transcript was significantly more abundant in the early (days 15-19) luteal phase than in the middle (days 20-23) or late (days 24-28) phases. To examine the hormonal regulation of StAR mRNA, corpora lutea were treated in vitro with increasing concentrations of human chorionic gonadotropin (hCG) or prostaglandin F2 alpha (PGF2 alpha). Following hCG stimulation, both 1.6- and 4.4-kb StAR transcripts were increased. A statistically significant increase of 2.2- and 1.8-fold in the 1.6-kb transcript was seen with hGC concentrations of 50 and 100 mIU/mL, respectively. This increase was coupled with a significant elevation in media progesterone levels, in contrast, PCF2 alpha treatment significantly decreased both StAR messenger ribonucleic acid (mRNA) expression and media progesterone levels at concentrations of 500 and 5000 ng/mL. This investigation demonstrated that StAR mRNA is regulated by tropic hormones and prostaglandins in the human corpus luteum. The parallel change in StAR mRNA in conjunction with a change in progesterone levels further supports StAR's putative role in the regulation of steroidogenesis.