Early membrane estrogenic effects required for full expression of slower genomic actions in a nerve cell line.
Interpretations of steroid hormone actions as slow, nuclear, transcriptional events have frequently been seen as competing against inferences of rapid membrane actions. We have discovered conditions where membrane-limited effects potentiate later transcriptional actions in a nerve cell line. Making use of a two-pulse hormonal schedule in a transfection system, early and brief administration of conjugated, membrane-limited estradiol was necessary but not sufficient for full transcriptional potency of the second estrogen pulse. Efficacy of the first pulse depended on intact signal transduction pathways. Surprisingly, the actions of both pulses were blocked by a classical estrogen receptor (ER) antagonist. Thus, two different modes of steroid hormone action can synergize.
Vasudevan
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Laboratory of Neurobiology and Behavior, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Kow
L M
LM
Pfaff
D W
DW
D000470:Alkaloids; D053119:Benzophenanthridines; D002118:Calcium / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D004967:Estrogens / Q000378:metabolism*; D000077267:Fulvestrant; D015870:Gene Expression; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D013873:Thionucleotides / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D053119:Benzophenanthridines; D002614:Chelating Agents; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D004967:Estrogens; D010617:Phenanthridines; D011960:Receptors, Estrogen; D013873:Thionucleotides; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D000077267:Fulvestrant; C016957:adenosine-3',5'-cyclic phosphorothioate; D004958:Estradiol; D004533:Egtazic Acid; D000242:Cyclic AMP; C016299:chelerythrine; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D002118:Calcium