Control of the steroidogenic machinery of the human trophoblast by cyclic AMP.
Human cytotrophoblasts express adenylate cyclase activity and possess membrane-bound regulatory proteins that bind guanine nucleotides (G proteins). Stimulation of the cyclase by forskolin or addition of 8-bromo-cAMP augments progesterone secretion by cultured cytotrophoblasts at least in part, by promoting accumulation of components of the cholesterol side-chain cleavage system. This is the consequence of increased synthesis of the proteins participating in steroidogenesis as a result of the 8-bromo-cAMP-provoked increase in their respective mRNAs. We propose that progesterone synthesis by cytotrophoblasts is up-regulated by cyclic AMP, which acts to increase expression of genes encoding the steroidogenic machinery. Paracrine or autocrine factors may initiate this cascade by stimulating the cytotrophoblast adenylate cyclase.
Nulsen
J C
JC
Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia 19104.
Silavin
S L
SL
Kao
L C
LC
Ringler
G E
GE
Kliman
H J
HJ
Strauss
J F
JF
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D005260:Female; D019204:GTP-Binding Proteins / Q000032:analysis; D006801:Humans; D011247:Pregnancy; D011374:Progesterone / Q000378:metabolism*; D014327:Trophoblasts / Q000032:analysis / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D011374:Progesterone; D000242:Cyclic AMP; D019204:GTP-Binding Proteins