Growth factors and phorbol-12-myristate-13-acetate modulate the follicle-stimulating hormone- and cyclic adenosine-3',5'-monophosphate-dependent regulation of 17beta-hydroxysteroid dehydrogenase type 1 expression in rat granulosa cells.
In the present study primary cultures of rat granulosa cells obtained from diethylstilbestrol (DES)-primed immature rats were used to study the regulation of 17beta-hydroxysteroid dehydrogenase (17HSD) activity and type 1 expression via protein kinase A (PKA)- and C (PKC)-dependent pathways, and by several autocrine and/or paracrine growth factors. Follicle-stimulating hormone (FSH), 8-bromo-cyclic adenosine-3',5'-monophosphate (8-Br-cAMP) and transforming growth factor beta1 (TGFbeta1) strongly enhanced 17HSD activity and type 1 expression. The stimulatory effects of FSH and 8-Br-cAMP were further potentiated by TGFbeta1. In contrast, neither phorbol-12-myristate-13-acetate (PMA), epidermal growth factor (EGF), transforming growth factor alpha (TGFalpha) nor fibroblast growth factor (bFGF) affected 17HSD activity or type 1 expression when given alone. However, they effectively neutralized the stimulatory effects of 8-Br-cAMP and FSH. The present data suggest that, in rat granulosa cells 17HSD type 1 expression is primarily induced by FSH acting via PKA-dependent pathway and the extent of the induction is modulated by PKC-dependent inhibition and autocrine/paracrine growth factors present in the ovary.
Kaminski
T
T
WHO Collaborating Center for Research in Human Reproduction and Department of Clinical Chemistry, University of Oulu, Finland.
Akinola
L
L
Poutanen
M
M
Vihko
R
R
Vihko
P
P
D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D000818:Animals; D001141:Aromatase / Q000235:genetics; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D004054:Diethylstilbestrol / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006107:Granulosa Cells / Q000201:enzymology*; D006133:Growth Substances / Q000494:pharmacology*; D011493:Protein Kinase C / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D004968:Estrogens, Non-Steroidal; D006133:Growth Substances; D012333:RNA, Messenger; D015124:8-Bromo Cyclic Adenosine Monophosphate; D004054:Diethylstilbestrol; D005640:Follicle Stimulating Hormone; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D001141:Aromatase; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate