Luteal expression of cytochrome P450 side-chain cleavage, steroidogenic acute regulatory protein, 3 beta-hydroxysteroid dehydrogenase, and 20 alpha-hydroxysteroid dehydrogenase genes in late pregnant rats: Effect of luteinizing hormone and RU486

A decrease in serum progesterone at the end of pregnancy is essential for t he induction of parturition in rats. We have previously demonstrated that L H participates in this process through: 1) inhibiting 3 beta -hydroxysteroi d dehydrogenase (3 beta -HSD) activity and 2) stimulating progesterone cata bolism by inducing 20 alpha -hydroxysteroid dehydrogenase (20 alpha -HSD) a ctivity. The objective of this investigation was to determine the effect of LH and progesterone on the luteal expression of the steroidogenic acute re gulatory protein (StAR), cytochrome P450 sidechain cleavage (P450(scc)), 3 beta -HSD, and 20 alpha -HSD genes. Gene expression was analyzed by Norther n blot analysis 24 and 48 h after administration of LH or vehicle on Day 19 of pregnancy. StAR and 3 beta -HSD mRNA levels were lower in LH-treated ra ts than in rats administered with vehicle at both time points studied. P450 (scc) mRNA levels were unaffected by LH. The 20 alpha -HSD mRNA levels were not different between LH and control rats 24 h after treatment; however, g reater expression of 20 alpha -HSD, with respect to controls, was observed in LH-treated rats 48 h after treatment. Luteal progesterone content droppe d in LH-treated rats at both time points studied, whereas serum progesteron e decreased after 48 h only. In a second set of experiments, the anti-proge sterone RU486 was injected intrabursally on Day 20 of pregnancy. RU486 had no effect on 3 beta -HSD or P450(scc) expression but increased 20 alpha -HS D mRNA levels after 8 h treatment. In conclusion, the luteolytic effect of LH is mediated by a drop in StAR and 3 beta -HSD expression without effect on P450(scc) expression. We also provide the first in vivo evidence indicat ing that a decrease in luteal progesterone content may be an essential step toward the induction of 20 alpha -HSD expression at the end of pregnancy i n rats.