Differential induction of hepatic estrogen receptor and vitellogenin gene transcription in Xenopus laevis.

Abstract

Low levels of estrogen receptor (200-500 per cell) are present in the liver of hormonally naive male Xenopus. However, administration of estradiol results in a rapid 2- to 5-fold increase in cellular estrogen receptor content concurrent with the de novo transcriptional activation of the genes for the yolk protein precursor vitellogenin. Studies on Xenopus embryogenesis suggest that estrogen receptor induction is required for the activation of vitellogenin transcription. The purpose of the present study was to examine the mechanism of estrogen receptor induction in male Xenopus liver. The experimental protocol used 4-hydroxytamoxifen, an antiestrogen with a high affinity for the estrogen receptor, to inhibit the effects of estradiol. Changes in estrogen receptor content were then determined through the use of an exchange assay. 4-Hydroxytamoxifen alone suppressed the level of estrogen receptor from 800 sites per cell in hormonally naive animals to 250 sites per cell. Administration of estradiol 24 h after the antiestrogen resulted in the induction of estrogen receptor to a level equivalent to that found in control animals (800 sites per cell). However, under the same conditions, estradiol was unable to overcome the antiestrogen inhibition of vitellogenin gene transcription. Although 4-hydroxytamoxifen displayed a high affinity for the hepatic estrogen receptor, it did not inhibit the binding of estradiol to a middle affinity cytoplasmic estrogen-binding protein. These results suggest that different mechanisms are involved in the induction of estrogen receptor and vitellogenin gene transcription.