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 E R and ER messenger RNA under different endocrine conditions. Hypophyse ctomy (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 g rowth 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) d oubled 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 m RNA 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 hormone s in HX animals. The glucocorticoid dexamethasone (DEX) alone increase d neither ER nor ER mRNA levels in HX animals. DEX and GH in combinati on 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 E R 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 a nd Tg in combination and almost 2-fold by DEX and GH in combination. I GF-I mRNA levels in HX rats were increased 4.5-iold by continuous infu sion 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 ac t directly on the liver to increase ER mRNA levels. GH, the most impor tant of these hormones, also acts at the translational and/or post-tra nslational level to increase ER protein levels. DEX treatment suppress es the stimulatory effects of T-3, but not of GH.