HORMONE AND PROSTAGLANDIN-F2-ALPHA REGULATION OF MESSENGER-RIBONUCLEIC-ACID ENCODING STEROIDOGENIC ACUTE REGULATORY PROTEIN IN HUMAN CORPORA-LUTEA

Steroidogenic acute regulatory (StAR) protein mediates the rapid incre ase in steroid hormone biosynthesis in response to tropic hormones by facilitating transport of cholesterol into the inner mitochondrial mem brane. Although our laboratory has recently reported on the hormonal r egulation of StAR mRNA in the rat ovary, the same regulation in the hu man corpus luteum requires analysis. To this end, a human StAR complem entary DNA (cDNA) probe of 858 bp was generated using reverse transcri ptase-PCR and RNA from human corpora lutea. The StAR sequence was conf irmed by dideoxy chain-termination sequence analysis. Northern blot an alysis using the StAR cDNA probe on human corpora lutea mRNA showed th at the probe hybridized to a major 1.6-kb transcript and a minor 4.4-k b transcript. Examination of corpora lutea of different luteal phases revealed that the basal expression of the 1.6-kb transcript was signif icantly more abundant in the early (days 15-19) luteal phase than in t he middle (days 20-23) or late (days 24-28) phases. To examine the hor monal regulation of StAR mRNA, corpora lutea were treated in vitro wit h increasing concentrations of human chorionic gonadotropin (hCG) or p rostaglandin F2 alpha (PGF2 alpha). Following hCG stimulation, both 1. 6- and 4.4-kb StAR transcripts were increased. A statistically signifi cant increase of 2.2- and 1.8-fold in the 1.6-kb transcript was seen w ith hGC concentrations of 50 and 100 mIU/mL, respectively. This increa se was coupled with a significant elevation in media progesterone leve ls, in contrast, PCF2 alpha treatment significantly decreased both StA R messenger ribonucleic acid (mRNA) expression and media progesterone levels at concentrations of 500 and 5000 ng/mL. This investigation dem onstrated that StAR mRNA is regulated by tropic hormones and prostagla ndins 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.