Catecholestrogen modulation of steroid production by rat luteal cells: mechanism of action.
This study investigated the mechanisms underlying 2-hydroxyestradiol (2-OHE2) effect on luteal steroidogenesis using serum-free cultures of mixed luteal cells from day 8 pseudopregnant rats. Initially, interactions between 2-OHE2 and LH or dibutyryl (db)cAMP on progesterone production were investigated. LH (250 ng/ml) and 2-OHE2 (2.5 microg/ml) had comparable effects on progesterone accumulation, while dbcAMP (5 mM) was more stimulatory. When applied together, 2-OHE2 did not synergize with LH or dbcAMP to further enhance progesterone accumulation. Furthermore, in time course experiments, the dose-dependent effect of 2-OHE2 was to reduce and eventually abolish the time-dependent increase in cAMP accumulation. In contrast LH stimulated cAMP accumulation at all times. Experiments in which cells were co-treated with 2-OHE2, 22-OH-cholesterol and cyanoketone, or with 2-OHE2 and 22-OH-cholesterol or pregnenolone indicated that 2-OHE2 not only had a stimulatory effect on the cholesterol side-chain cleavage and 3beta-hydroxysteroid dehydrogenase enzymes, but it also appeared to inhibit the 20alpha-hydroxysteroid dehydrogenase leading to a relative increase in progesterone accumulation. Experiments with hormone antagonists suggested that the actions of 2-OHE2 were not mediated by the estrogen, alpha- or beta-adrenergic receptors. The results of this study support the concept of a physiological role for catecholestrogens in rat luteal steroidogenesis.
Tekpetey
F R
FR
Department of Physiology, The University of Western Ontario, London, Canada.
Armstrong
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DT
D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002393:Estrogens, Catechol / Q000494:pharmacology*; D005260:Female; D008184:Luteal Cells / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013256:Steroids / Q000096:biosynthesis*
D002393:Estrogens, Catechol; D013256:Steroids; D004958:Estradiol; C001390:2-hydroxyestradiol; D000242:Cyclic AMP