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, transcriptiona l events have frequently been seen as competing against inferences of rapid membrane actions. We have discovered conditions where membrane-limited eff ects potentiate later transcriptional actions in a nerve cell line. Making use of a two-pulse hormonal schedule in a transfection system, early and br ief 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 p athways. Surprisingly, the actions of both pulses were blocked by a classic al estrogen receptor (ER) antagonist. Thus, two different modes of steroid hormone action can synergize.