Effects of adenine nucleotides on choriogonadotropin alpha and beta subunit synthesis.
The alpha subunit of human chorionic gonadotropin (CG) contains a discrete cAMP response element in the 5' flanking region of the gene. Since cAMP also stimulates the synthesis of the CG beta subunit the presence of a cAMP cis element in the CG beta gene was examined. Deletion mutants bearing various lengths of CG beta 5' region in front of the chloramphenicol acetyl transferase (CAT) gene were transfected in placental tumor cells. No discrete cAMP response element could be identified. Unexpectedly we also observed that AMP and adenosine not only stimulated CAT activity driven by CG beta promoter sequences but also enhanced synthesis of CG alpha and beta subunits in cultured choriocarcinoma cells. GMP, CMP, guanosine, and cytosine were inactive at comparable concentrations. These data suggest that the response of the CG alpha and beta genes to the non-cyclic adenine derivatives occurs by a mechanism that differs from cAMP.
Otani
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Department of Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110.
Otani
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Boime
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D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000227:Adenine Nucleotides / Q000494:pharmacology*; D000241:Adenosine / Q000494:pharmacology; D000249:Adenosine Monophosphate / Q000494:pharmacology; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D002822:Choriocarcinoma / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000096:biosynthesis* / Q000235:genetics; D018997:Chorionic Gonadotropin, beta Subunit, Human; D000242:Cyclic AMP / Q000494:pharmacology; D005260:Female; D015292:Glycoprotein Hormones, alpha Subunit / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007163:Immunosorbent Techniques; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000235:genetics; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000378:metabolism
D000227:Adenine Nucleotides; D006063:Chorionic Gonadotropin; D018997:Chorionic Gonadotropin, beta Subunit, Human; D015292:Glycoprotein Hormones, alpha Subunit; D010446:Peptide Fragments; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000249:Adenosine Monophosphate; D000242:Cyclic AMP; D015500:Chloramphenicol O-Acetyltransferase; D000241:Adenosine