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Luteal Expression of Cytochrome P450 Side-Chain Cleavage, Steroidogenic Acute Regulatory Protein, 3ß-Hydroxysteroid Dehydrogenase, and 20-Hydroxysteroid Dehydrogenase Genes in Late Pregnant Rats: Effect of Luteinizing Hormone and RU486¹

^a Laboratorio de Reproducción y Lactancia, CONICET, 5500 Mendoza, Argentina ^b Department of Obstetrics, Gynecology & Reproductive Sciences, University of Saskatchewan, Saskatoon, Canada S7N 0W8

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 3ß-hydroxysteroid dehydrogenase (3ß-HSD) activity and 2) stimulating progesterone catabolism by inducing 20-hydroxysteroid dehydrogenase (20-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), 3ß-HSD, and 20-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 3ß-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 20-HSD mRNA levels were not different between LH and control rats 24 h after treatment; however, greater expression of 20-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 3ß-HSD or P450_scc expression but increased 20-HSD mRNA levels after 8 h treatment. In conclusion, the luteolytic effect of LH is mediated by a drop in StAR and 3ß-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 20-HSD expression at the end of pregnancy in rats.

FOOTNOTES

First decision: 20 March 2001.

¹ This work was supported by grant PMT-PICT0098 from Agencia Nacional de Promoción Científica y Tecnológica and by grant PLI 325/8 PRE 023/98 from the PLACIRH (Programa Latinoamericano de Capacitación e Investigación en Reproducción Humana) to C.O.S. and grants from the Natural Science and Engineering Research Council of Canada and Canadian Institute of Health Science/Saskatchewan Health Regional Partnership to J.C.

² Correspondence: Carlos O. Stocco, Department of Physiology and Biophysics (M/C 901), University of Illinois at Chicago, 835 South Wolcott Avenue, Chicago, IL 60612-7342. FAX: 312 413 0159; costocco{at}uic.edu

³ Reprint requests: Ricardo P. Deis, Laboratorio de Reproducción y Lactancia, LARLAC-CONICET, Casilla de Correo 855, 5500 Mendoza, Argentina.

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