Regulation of aromatase activity in FSH-primed rat granulosa cells in vitro by follicle-stimulating hormone and various amounts of human chorionic gonadotrophin.
The influence of various amounts of human chorionic gonadotrophin (HCG), with or without follicle-stimulating hormone (FSH), on aromatase activity, progesterone- and cAMP-accumulation in rat granulosa cells was investigated. Cells were isolated from immature diethylstilbestrol-treated rats and primed for 2 days in vitro with FSH (50 mIU/ml) to give a maximum response of the cells with respect to the induction of aromatase activity. After FSH priming, small amounts of HCG (1-5 mIU/ml) increased aromatase activity during an additional culture period of 24 h, with a maximum of 4- to 5-fold at 5-8 mIU/ml HCG. At higher concentrations of HCG, aromatase activity declined reaching a plateau (1.5-fold stimulation) at 20 mIU/ml HCG. When HCG was combined with FSH (50 mIU/ml) following the priming period, aromatase activity was stimulated in an additive way, reaching a maximum at 4-5 mIU/ml HCG followed by a decline, similar to that seen in the absence of FSH. HCG induced a dose-dependent increase in cAMP with a maximum at 20 mIU/ml. This increase in cAMP was higher when HCG was combined with FSH. Aromatase activity was inhibited by 3-isobutyl-methyl-xanthine and forskolin, both of which induce elevated cAMP levels in the cell. HCG, and HCG in combination with FSH, increased the production of progesterone in a dose-dependent manner until a plateau was reached. In the presence of FSH, this plateau was reached at lower HCG concentrations. Both R5020 and progesterone showed dose-dependent inhibition of aromatase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Overes
H W
HW
Organon International, Scientific Development Group, Oss, The Netherlands.
de Leeuw
R
R
Kloosterboer
H J
HJ
D000818:Animals; D001141:Aromatase / Q000378:metabolism*; D047072:Aromatase Inhibitors; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D006107:Granulosa Cells / Q000187:drug effects* / Q000201:enzymology; D006080:Ovarian Follicle / Q000502:physiology*; D011374:Progesterone / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D047072:Aromatase Inhibitors; D006063:Chorionic Gonadotropin; D011374:Progesterone; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP; D001141:Aromatase