THE HORMONAL-REGULATION OF THE ESTROGEN-RECEPTOR IN RAT-LIVER - AN INTERPLAY INVOLVING GROWTH-HORMONE, THYROID-HORMONES AND GLUCOCORTICOIDS

The regulation of the formation of the hepatic oestrogen receptor (ER) in adult female rats was studied by assaying steady state levels of ER and ER messenger RNA under different endocrine conditions. Hypophysectomy (HX) drastically reduced ER levels from 67.5+/-7.9 to 8.4+/-0.5 (means +/- S.E.M.) fmol/mg cytosolic protein. Continuous infusion of growth hormone (GH) to HX animals tripled ER and doubled ER mRNA levels. Treatment with triiodothyronine (T-3) in a high dose (10 g/day mu) doubled ER mRNA levels. The effects of T-3 were dose-dependent, since a lower dose (1 mu g/day) increased neither ER nor ER mRNA levels. ER mRNA concentrations were increased by GH to 481+/-44% and by T-3 to 372+/-35% of HX control levels 4 h after single injections of the hormones in HX animals. The glucocorticoid dexamethasone (DEX) alone increased neither ER nor ER mRNA levels in HX animals. DEX and GH in combination increased ER 5-fold and ER mRNA 2-fold compared with control levels in HX animals, whereas DEX and T-3 in combination increased neither ER nor ER mRNA levels. Treatment with prolactin affected neither ER nor ER mRNA levels in HX rats. Insulin-like growth factor I (IGF-I) mRNA and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA levels were measured. GAPDH mRNA levels were increased 25-fold in HX rats by DEX and Tg in combination and almost 2-fold by DEX and GH in combination. IGF-I mRNA levels in HX rats were increased 4.5-iold by continuous infusion of GH alone, 6-fold by GH and T-3 in combination, and 25-fold by GH and DEX in combination. These data indicate that both GH and T-3 act directly on the liver to increase ER mRNA levels. GH, the most important of these hormones, also acts at the translational and/or post-translational level to increase ER protein levels. DEX treatment suppresses the stimulatory effects of T-3, but not of GH.