PROSTAGLANDIN-F2-ALPHA REDUCES STEROIDOGENIC ACUTE REGULATORY (STAR) PROTEIN MESSENGER-RIBONUCLEIC-ACID EXPRESSION IN THE RAT OVARY

Steroid biosynthesis begins with the enzymatic conversion of cholester ol to pregnenolone. This reaction is catalyzed by the cytochrome P450 side-chain cleavage enzyme (P450scc), which is located on the matrix s ide of the inner mitochondrial membrane, Although the rate-limiting en zymatic step in steroidogenesis is the conversion of cholesterol to pr egnenolone by the side-chain cleavage enzyme, the true rate-limiting s tep in this process is the delivery of cholesterol to the inner mitoch ondrial membrane. Steroidogenic acute regulatory (StAR) protein is tho ught to mediate the rapid increase in steroid hormone biosynthesis in response to tropic hormones by facilitating cholesterol transport to t he inner mitochondrial membrane, Cholesterol transport across the inne r mitochondrial membrane has also been implicated as the target for pr ostaglandin F2 alpha's (PCF2 alpha) antisteroidogenic activity. Since cholesterol delivery to the P450scc is a rapidly regulated step in ste roidogenesis, StAR mRNA levels were examined after the administration of a luteolytic injection of PCF2 alpha. The results of this investiga tion revealed that both major StAR RNA transcripts were decreased in t he ovary, 10 d after ovulation, following PGF2 alpha administration. S erum progesterone levels were decreased Following PGF2 alpha administr ation in parallel with the decreased expression of StAR. Following PGF 2 alpha treatment, ovarian StAR transcripts at 3.4 and 1.6 kb were red uced 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 PGF2 alpha injection. Time course experiments following PGF2 alpha adminis tration showed a significant decrease in StAR expression as early as 3 0 min (p < 0.02) following injection, In contrast to StAR's expression after PGF2 alpha administration, StAR mRNA levels were elevated in re sponse to human chorionic gonadotropin (hCG) 3 h postinjection, Admini stration of PGF2 alpha followed by hCG injection effectively blocked i nduction of StAR expression, StAR mRNA levels were reduced 1.5-fold re lative to control animals and 3.5-fold relative to the hCG-treated ani mals (p < 0.05). The levels of serum progesterone paralleled the chang e in ovarian StAR mRNA in all experiments, This study provides the fir st 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.