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)