Prostaglandin F2α reduces steroidogenic acute regulatory (StAR) protein messenger ribonucleic acid expression in the rat ovary

Steroid biosynthesis begins with the enzymatic conversion of cholesterol to pregnenolone. This reaction is catalyzed by the cytochrome P450 side-chain cleavage enzyme (P450scc), which is located on the matrix side of the inner mitochondrial membrane. Although the rate-limiting enzymatic step in steroidogenesis is the conversion of cholesterol to pregnenolone by the side-chain cleavage enzyme, the true rate-limiting step in this process is the delivery of cholesterol to the inner mitochondrial membrane. Steroidogenic acute regulatory (StAR) protein is thought to mediate the rapid increase in steroid hormone biosynthesis in response to tropic hormones by facilitating cholesterol transport to the inner mitochondrial membrane. Cholesterol transport across the inner mitochondrial membrane has also been implicated as the target for prostaglandin F2α's (PGF2α) antisteroidogenic activity. Since cholesterol delivery to the P450scc is a rapidly regulated step in steroidogenesis, StAR mRNA levels were examined after the administration of a luteolytic injection of PGF2α. The results of this investigation revealed that both major StAR RNA transcripts were decreased in the ovary, 10 d after ovulation, following PGF2α administration. Serum progesterone levels were decreased following PGF2α administration in parallel with the decreased expression of StAR. Following PGF2α treatment, ovarian StAR transcripts at 3.4 and 1.6 kb were reduced 4-fold (p<0.01) and 2.5-fold (p<0.025), respectively, after 4 h. Ovarian P450scc mRNA levels were also reduced (70%) 4 h after PGF2α injection. Time course experiments following PGF2α administration showed a significant decrease in StAR expression as early as 30 min (p<0.02) following injection. In contrast to StAR's expression after PGF2α administration, StAR mRNA levels were elevated in response to human chorionic gonadotropin (hCG) 3 h postinjection. Administration of PGF2α followed by hCG injection effectively blocked induction of StAR expression. StAR mRNA levels were reduced 1.5-fold relative to control animals and 3.5-fold relative to the hCG-treated animals (p<0.05). The levels of serum progesterone paralleled the change in ovarian StAR mRNA in all experiments. This study provides the first evidence that StAR mRNA expression is mediated by prostaglandins in the rat ovary further supporting its important role in the regulation of steroid hormone biosynthesis.