title: Epidermal growth factor but not insulin-like growth factor-I potentiates adenosine 3',5'-monophosphate-mediated chorionic gonadotropin secretion by cultured human choriocarcinoma cells.
abstract: Epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) regulate hormone production in several endocrine cells cultures. We have previously found that 12-O-tetradecanoyl phorbol-13-acetate (TPA), a protein kinase C activator, potentiates the cAMP-mediated secretion of human CB (hCG) in cultured human choriocarcinoma cells. We have now studied whether EGF and IGF-I modify cAMP-mediated hCG secretion in JEG-3 cells, which possess high affinity receptors to these growth factors. EGF, TPA, and cholera toxin (CT), an activator of adenylate cyclase, stimulated the secretion of hCG in a concentration-dependent manner during a 24-h culture period. The maximal effective concentrations of EGF (10 ng/ml), TPA (10 ng/ml), and CT (1.0 ng/ml) exerted 2.3-, 2.4-, and 3.9-fold increase over unstimulated level, respectively. EGF and TPA potentiated the effect of CT on hCG secretion from 3.9- to 7.8-fold and from 3.9- to 14.8-fold, respectively. By contrast, IGF-I was ineffective. During a 24-h culture, EGF and TPA potentiated the effect of CT on cAMP accumulation 1.4-fold and 1.3-fold over the production of CT-treated cells. Time-course studies indicated that these effects on cAMP and hCG were detectable at 3 h and 6 h, and they continued to increase up to 48 h and 72 h, respectively. When added alone, EGF and TPA increased cAMP production y 2.0-fold and 2.5-fold over controls at 24 h. Again, IGF-I was ineffective. Moreover, EGF and TPA potentiated the effect of 8-bromo-cAMP (on hCG production to a similar extent than they did to CT-stimulated hCG production. The binding of [125I]iodo-EGF to the cells was not altered by a 48-h CT-treatment whereas the binding of [125I]iodo-IGF-I was increased by 2.1-fold above untreated cells. Our data show that both EGF and TPA potentiated the effect of CT on hCG secretion in JEG-3 cells, whereas IGF-I had no effect. Although EGF and TPA facilitated CT-stimulated cAMP accumulation, their site of action on cAMP-mediated hCG production is distinct from the adenylate cyclase or EGF-receptor level since EGF and TPA potentiated the hCG secretion stimulated by 8-bromo-cAMP and an increase in cAMP production did not alter the binding properties of EGF-receptor.
authors.affiliation: Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Finland.
authors.forename: O
authors.initials: O
authors.lastname: Ritvos
authors.forename: J
authors.initials: J
authors.lastname: Jalkanen
authors.forename: F
authors.initials: F
authors.lastname: Pekonen
authors.forename: U H
authors.initials: UH
authors.lastname: Stenman
authors.forename: T
authors.initials: T
authors.lastname: Ranta
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D001667:Binding, Competitive; D002772:Cholera Toxin / Q000494:pharmacology; D002822:Choriocarcinoma / Q000378:metabolism*; D006063:Chorionic Gonadotropin / Q000378:metabolism*; D000242:Cyclic AMP / Q000502:physiology*; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007700:Kinetics; D013002:Somatomedins / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D006063:Chorionic Gonadotropin; D013002:Somatomedins; D015124:8-Bromo Cyclic Adenosine Monophosphate; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D002772:Cholera Toxin; D000242:Cyclic AMP; D066246:ErbB Receptors; D013755:Tetradecanoylphorbol Acetate