Actions of LH/hCG on accumulation and catabolism of progestins in cultured rat granulosa cells.
Immature hypophysectomized rats were treated with estradiol-17 beta and follicle-stimulating hormone. Granulosa cells were isolated and incubated for 24 h with or without varying doses of ovine luteinizing hormone (NIMADD-oLH-24) or human chorionic gonadotropin (NIADDK CR 125) and accumulations of progesterone and 20 alpha-hydroxy-4-pregnen-3-one were determined. The cells were reincubated for 3 h with [4-14C]progesterone (0.5 nmol/mL) and the radiolabelled metabolites were separated and quantified. Both LH (0.04-1.0 ug/mL) and hCG (0.04-1.0 ug/mL) enhanced the accumulation of endogenous progesterone (by up to 300 and 150%, respectively) and 20 alpha-hydroxy-4-pregnen-3-one (by up to 90 and 85%, respectively) producing dose-dependent increases of the ratio of progesterone to 20 alpha-hydroxy-4-pregnen-3-one (by up to 125 and 70%, respectively). Studies of the metabolism of [1-14C] progesterone have demonstrated that both LH and hCG led to a dose-dependent decrease of the utilization of radiolabelled progesterone (down to 64 and 70%, respectively, of the control value). This effect was associated with an LH- and hCG-dependent inhibition of 20 alpha-hydroxysteroid dehydrogenase activity (down to 60 and 70%, respectively, of the control value) but had no significant effect on 5 alpha-reductase. The present results indicate that LH and hCG stimulate accumulation of progesterone at least in part by decreasing the 20 alpha-hydroxysteroid dehydrogenase activity.
Moon
Y S
YS
Duleba
A J
AJ
Yuen
B H
BH
D015089:20-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors; D004092:20-alpha-Dihydroprogesterone / Q000378:metabolism*; D043607:20-alpha-Hydroxysteroid Dehydrogenase; D000818:Animals; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000494:pharmacology*; D011374:Progesterone / Q000031:analogs & derivatives* / Q000378:metabolism*; D051381:Rats
D006063:Chorionic Gonadotropin; D004092:20-alpha-Dihydroprogesterone; D011374:Progesterone; D007986:Luteinizing Hormone; D015089:20-Hydroxysteroid Dehydrogenases; D043607:20-alpha-Hydroxysteroid Dehydrogenase