Hormone and prostaglandin F2 alpha regulation of messenger ribonucleic acid encoding steroidogenic acute regulatory protein in human corpora lutea

Abstract

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 hCG concentrations of 50 and 100 mIU/mL, respectively. This increase was coupled with a significant elevation in media progesterone levels. In contrast, PGF2 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.