Effects of 8-bromo-cAMP on expression of endocrine functions by cultured human trophoblast cells. Regulation of specific mRNAs.
There is little information on the molecular events underlying the effects of cAMP on human chorionic gonadotropin (hCG) and particularly steroidal hormone production in normal trophoblasts. We examined the effects of 8-bromo-cAMP on mRNAs encoding two components of the cholesterol side-chain cleavage system, cytochrome P-450scc and adrenodoxin, and the alpha- and beta-subunits of hCG in cultured cytotrophoblasts. cAMP caused an increase in all of these mRNAs within 24 h, whereas actin mRNA declined. alpha-hCG mRNA increased first, followed by adrenodoxin, beta-hCG and cytochrome P-450scc mRNAs. The effects of 8-bromo-cAMP on alpha- and beta-hCG, adrenodoxin, and cytochrome P-450scc mRNAs, in cytotrophoblasts and JEG-3 choriocarcinoma cells, required the catalytic unit of protein kinases since H-7, a kinase inhibitor, blocked the increase in the mRNAs and prevented the stimulation of hCG and progesterone secretion. 8-Bromo-cAMP promoted a rapid increase in alpha-hCG mRNA in cytotrophoblasts in the presence of cycloheximide, an inhibitor of protein synthesis. In cytotrophoblasts, cycloheximide reduced basal and 8-bromo-cAMP-stimulated adrenodoxin mRNA abundance. In contrast, basal and cAMP-stimulated adrenodoxin mRNA was augmented by cycloheximide in JEG-3 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Ringler
G E
GE
Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia.
Kao
L C
LC
Miller
W L
WL
Strauss
J F
JF
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D000199:Actins / Q000235:genetics / Q000378:metabolism; D000325:Adrenodoxin / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D002822:Choriocarcinoma; D006063:Chorionic Gonadotropin / Q000235:genetics* / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D015342:DNA Probes; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism* / Q000502:physiology; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism*
D000199:Actins; D006063:Chorionic Gonadotropin; D015342:DNA Probes; D012333:RNA, Messenger; D000325:Adrenodoxin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003577:Cytochrome P-450 Enzyme System; D011494:Protein Kinases