INDUCTION OF THE ESTROGEN-RECEPTOR BY GROWTH-HORMONE AND GLUCOCORTICOID SUBSTITUTION IN PRIMARY CULTURES OF RAT HEPATOCYTES

Hepatic estrogen receptors (ER) mediate estrogenic effects on mammalian liver metabolism and are thereby involved in the regulation of important physiological/pathological processes, such as coagulation, atherosclerosis, and hypertension. The regulation of the formation of the ER in primary cultures of rat hepatocytes was studied by assaying ER and ER mRNA under different endocrine conditions. The ER concentration was measured using two different methods, a ligand-binding technique and an ER enzyme immunoassay. The results obtained by the two methods showed good correlation, and linear regression analysis gave a correlation coefficient of 0.95. ER concentrations fell to low steady state levels within 16 h after establishing the cell culture and remained low in the absence of hormonal substitution. Upon medium supplementation with pituitary GH and the glucocorticoid dexamethasone (DEX) in combination, the ER concentration increased 6-fold from 4.2 +/- 1.0 to 25.8 +/- 7.0 fmol/mg cytosolic protein. ER mRNA was measured by solution hybridization. Substitution with GH and DEX in combination increased ER mRNA to 210 +/- 14% of control levels. No effect on ER mRNA stability was seen after hormone treatment. It is concluded that the regulatory effects of GH and DEX on the hepatic ER in this in vitro system are very similar to the effects of these hormones under in vivo conditions. The inducible expression of the ER has never before, to our knowledge, been demonstrated in any mammalian liver cell culture system.