title: Luteal expression of cytochrome P450 side-chain cleavage, steroidogenic acute regulatory protein, 3beta-hydroxysteroid dehydrogenase, and 20alpha-hydroxysteroid dehydrogenase genes in late pregnant rats: effect of luteinizing hormone and RU486.
abstract: A decrease in serum progesterone at the end of pregnancy is essential for the induction of parturition in rats. We have previously demonstrated that LH participates in this process through: 1) inhibiting 3beta-hydroxysteroid dehydrogenase (3beta-HSD) activity and 2) stimulating progesterone catabolism by inducing 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) activity. The objective of this investigation was to determine the effect of LH and progesterone on the luteal expression of the steroidogenic acute regulatory protein (StAR), cytochrome P450 side-chain cleavage (P450(scc)), 3beta-HSD, and 20alpha-HSD genes. Gene expression was analyzed by Northern blot analysis 24 and 48 h after administration of LH or vehicle on Day 19 of pregnancy. StAR and 3beta-HSD mRNA levels were lower in LH-treated rats than in rats administered with vehicle at both time points studied. P450(scc) mRNA levels were unaffected by LH. The 20alpha-HSD mRNA levels were not different between LH and control rats 24 h after treatment; however, greater expression of 20alpha-HSD, with respect to controls, was observed in LH-treated rats 48 h after treatment. Luteal progesterone content dropped in LH-treated rats at both time points studied, whereas serum progesterone decreased after 48 h only. In a second set of experiments, the anti-progesterone RU486 was injected intrabursally on Day 20 of pregnancy. RU486 had no effect on 3beta-HSD or P450(scc) expression but increased 20alpha-HSD mRNA levels after 8 h treatment. In conclusion, the luteolytic effect of LH is mediated by a drop in StAR and 3beta-HSD expression without effect on P450(scc) expression. We also provide the first in vivo evidence indicating that a decrease in luteal progesterone content may be an essential step toward the induction of 20alpha-HSD expression at the end of pregnancy in rats.
authors.affiliation: Laboratorio de Reproducción y Lactancia, CONICET, 5500 Mendoza, Argentina. costocco@uic.edu
authors.forename: C O
authors.initials: CO
authors.lastname: Stocco
authors.forename: J
authors.initials: J
authors.lastname: Chedrese
authors.forename: R P
authors.initials: RP
authors.lastname: Deis
mesh_terms: D015089:20-Hydroxysteroid Dehydrogenases / Q000235:genetics*; D043607:20-alpha-Hydroxysteroid Dehydrogenase; D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics*; D000818:Animals; D015152:Blotting, Northern; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics*; D003338:Corpus Luteum / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D005865:Gestational Age; D006727:Hormone Antagonists / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D010750:Phosphoproteins / Q000235:genetics*; D011247:Pregnancy; D011374:Progesterone / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D006727:Hormone Antagonists; D010750:Phosphoproteins; D012333:RNA, Messenger; D000098682:Steroidogenic Acute Regulatory Protein; D015735:Mifepristone; D011374:Progesterone; D007986:Luteinizing Hormone; D015096:3-Hydroxysteroid Dehydrogenases; D015089:20-Hydroxysteroid Dehydrogenases; D043607:20-alpha-Hydroxysteroid Dehydrogenase; D002786:Cholesterol Side-Chain Cleavage Enzyme