Non-genomic effects of estrogens and antiestrogens

Abstract

In addition to the effects of estrogens on transcription, mediated by the estrogen receptor, and the antiestrogenic effects of triphenylethylene derivatives resulting from their competitive action at the estrogen receptor level, estrogens and antiestrogens can affect cellular processes though other mechanisms. Estrogens can bind and alter enzymatic activities in membranes isolated from target cells, can influence the activities of purified enzymes and can change cell permeability and polarization under conditions excluding transcriptional effects. Triphenylethylene antiestrogens at micromolar concentrations can affect cholinergic, histaminergic and dopaminergic systems, affect calmodulin action and influence protein kinase C activity. Tamoxifen added to suspension of human endometrial adenocarcinoma cells at concentrations greater than 10 microM both increased phosphoinositide hydrolysis and inhibited the stimulatory effect of carbachol on this system. These effects, however, may represent nonspecific actions of the antiestrogens, shared with the structurally related phenothiazines, on the plasma membrane.