Levonorgestrel inhibits luteinizing hormone-stimulated progesterone production in rat luteal cells.
The effects of the synthetic progestin levonorgestrel (LNG) on basal and LH-stimulated progesterone production were studied in collagenase-dispersed luteal cells obtained from 9-day pregnant rats. Luteal cells responded to ovine LH (oLH) with an increase in progesterone output which was maximal at a dose of 100 ng/ml. No effect of LNG was observed at 0.1-10 microM, but at 100 microM, it inhibited basal progesterone production. On the other hand, a dose of 10 microM LNG suppressed the stimulation of progesterone secretion induced by oLH, dibutyryl-cAMP and pregnenolone. It is suggested that the possible mechanism of action of the progestin involves a post-cAMP site and, in some way, may lead to an interference with 3 beta-hydroxysteroid dehydrogenase activity, which catalyzes the formation of progesterone from pregnenolone, the last step of progesterone biosynthesis. This study provides a different point of view supporting an autocrine control mechanism by which progesterone, the principal steroidogenic product of luteal cells, may exert a negative ultra-short loop regulation of its own biosynthesis.
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CM
Laboratorio de Reproducción y Lactancia, CONICET, Mendoza, Argentina.
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DG
Deis
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D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D003338:Corpus Luteum / Q000378:metabolism*; D005260:Female; D016912:Levonorgestrel / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000037:antagonists & inhibitors*; D010053:Ovary / Q000378:metabolism; D011247:Pregnancy; D011284:Pregnenolone / Q000494:pharmacology; D011374:Progesterone / Q000096:biosynthesis*; D051381:Rats
D011374:Progesterone; D016912:Levonorgestrel; D003994:Bucladesine; D011284:Pregnenolone; D007986:Luteinizing Hormone