Polyamines control human chorionic gonadotropin production in the JEG-3 choriocarcinoma cell.
The effect of inhibition of ornithine decarboxylase with difluoromethylornithine (DFMO) and the resultant lowering of polyamine levels upon human chorionic gonadotropin (hCG) production in JEG-3 choriocarcinoma cells was investigated. DFMO (10 mM) totally inhibited ornithine decarboxylase activity. In DFMO-treated cells, cellular spermidine concentrations fell to nondetectable levels (less than 1% of control values) within 24 h and spermine concentrations were reduced to 41.9% of controls over 6 days. DFMO caused a 70-80% inhibition of hCG production. Levels of mRNA for both the alpha and beta subunits of hCG were also inhibited relative to mRNA for tubulin. Exogenous putrescine normalized hCG production in a dose-dependent manner. Other diamines, including cadaverine, 1,3-diaminopropane, 1,6-diaminohexane, and 1,7-diaminoheptane, were ineffective in reestablishing hCG production in DFMO-treated cells. Dibutyryl cAMP (1 mM) stimulated hCG production and increased levels of mRNA for the alpha and beta subunit 5-40-fold in both DFMO-treated and control cells. Polyamines appear to have a fundamental role in hCG production in JEG-3 choriocarcinoma cells. However, dibutyryl cAMP can partially overcome or circumvent the requirement for polyamines in hCG biosynthesis.
Moore
J J
JJ
Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio 44109.
Lundgren
D W
DW
Moore
R M
RM
Andersen
B
B
D003994:Bucladesine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002822:Choriocarcinoma / Q000378:metabolism*; D006063:Chorionic Gonadotropin / Q000096:biosynthesis* / Q000235:genetics; D000518:Eflornithine / Q000494:pharmacology; D006801:Humans; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000502:physiology*; D011700:Putrescine / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013095:Spermidine / Q000378:metabolism; D013096:Spermine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D006063:Chorionic Gonadotropin; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D012333:RNA, Messenger; D013096:Spermine; D003994:Bucladesine; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine