Thyroid hormone and glucocorticoid independently regulate the expression of estrogen receptor in male Xenopus liver cells.

Earlier studies from our laboratory had shown that triiodothyronine (T-3) strongly potentiates the activation by estradiol (E(2)) of silent vitellogenin (Vit) genes and the autoinduction of estrogen receptor (ER) mRNA in primary cultures of male Xenopus hepatocytes (Rabelo and Tata, 1993). It was, however, not known if T-3, or other hormones, could up-regulate ER mRNA in the absence of exogenous E(2). We now show that T-3 and dexamethasone (Dex), but not progesterone and testosterone, directly induce ER mRNA within 4 h by separate pathways, at doses compatible with the K-d values of their receptors. This induction of ER mRNA is accompanied by a marked enhancement of the activation of the silent Vit B1 gene if E(2) is added by 12 h after T-3 and Dex, thus suggesting an elevated level of functional ER induced by the two hormones. This conclusion was supported by a higher rate of transcription from an estrogen response element (ERE)-tk-CAT construct transfected into cultured hepatocytes pre-treated with T-3 and Dex before incubation with estrogen. Our findings emphasize the importance of hormonal interplay via auto- and cross-regulation of nuclear hormone receptors.