Luteolytic action of RU486: modulation of luteal 3 beta-hydroxysteroid dehydrogenase and 20 alpha-hydroxysteroid dehydrogenase activities in late pregnant rats.
The effect of the synthetic antiprogestin RU486 on luteal function in late pregnant rats was studied by evaluating the activities of the enzymes 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) and 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD). RU486 (2 mg/kg) administered to rats on day 18 of pregnancy at 10.00 h induced preterm delivery 26.4 +/- 0.35 h (n = 8) after treatment. Luteal 3 beta-HSD activity increased 24 and 34 h after RU486 injection, but a significant and progressive decrease started at 48 h with the maximal reduction 72 h after RU486 treatment, when compared with controls. Serum progesterone concentration decreased at the time of 3 beta-HSD activity reduction. Interestingly, 20 alpha-HSD activity started to increase 58 h after RU486 injection. The administration of the cyclooxygenase inhibitor, diclofenac (1.3 mg/kg), on days 17-19 of pregnancy to RU486-treated rats, delayed abortion and the duration of delivery, and prevented the decrease in 3 beta-HSD and the increase in 20 alpha-HSD activities observed 58 h after antiprogesterone treatment. RU486 administered intrabursally (1 microgram per ovary) on day 20 (14.00-15.00 h) increased 3 beta-HSD and decreased 20 alpha-HSD luteal activities at 18.00 h on day 21 of pregnancy, without modifying serum progesterone concentration, when compared with normal pregnant rats. In conclusion, the luteolytic process after preterm delivery induced by RU486 administration in late pregnant rats is characterized by a decrease in luteal 3 beta-HSD activity and circulating progesterone, which may trigger the increase in luteal 20 alpha-HSD activity. Prostaglandins seems to be involved in the increase of 20 alpha-HSD activity and therefore, in the demise of corpora lutea.
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Laboratorio de Reproducción y Lactancia, CRICYT-CONICET, Mendoza, Argentina.
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D015089:20-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D043607:20-alpha-Hydroxysteroid Dehydrogenase; D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D000818:Animals; D003338:Corpus Luteum / Q000187:drug effects* / Q000201:enzymology*; D004008:Diclofenac / Q000494:pharmacology; D005260:Female; D003341:Luteolysis / Q000187:drug effects / Q000378:metabolism; D008186:Luteolytic Agents / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology*; D007752:Obstetric Labor, Premature / Q000097:blood / Q000139:chemically induced / Q000201:enzymology; D011247:Pregnancy; D011374:Progesterone / Q000097:blood; D051381:Rats; D017208:Rats, Wistar
D008186:Luteolytic Agents; D004008:Diclofenac; D015735:Mifepristone; D011374:Progesterone; D015096:3-Hydroxysteroid Dehydrogenases; D015089:20-Hydroxysteroid Dehydrogenases; D043607:20-alpha-Hydroxysteroid Dehydrogenase