Transient administration of estradiol-17 beta establishes an autoregulatory loop permanently inducing estrogen receptor mRNA.

A single transient dose of estradiol-17 beta is sufficient to elicit the permanent induction of hepatic estrogen receptor mRNA, which is induced 18-fold (from 0.13 to 2.4 molecules per cell) and then remains fully induced for at least 125 days. In primary liver cultures, extremely low concentrations of estradiol-17 beta, which are below the Kd of the Xenopus laevis estrogen receptor, maintain persistent induction of estrogen receptor mRNA but not of estrogen-inducible vitellogenin mRNA. These data and the ability of the antiestrogen, hydroxytamoxifen, to reverse persistent induction of estrogen receptor mRNA, support a model in which transient doses of estradiol-17 beta induce the estrogen receptor and thereby establish an autoregulatory loop. The low levels of estradiol-17 beta normally circulating in male X. laevis and the elevated level of receptor provide sufficient hormone-receptor complex to permanently maintain the induced level of expression of the estrogen receptor gene. The permanent induction of the estrogen receptor may be the regulatory switch that results in the persistent expression of a recently identified class of proteins that exhibit long-term responses to estrogen.