Effects of sex hormones on the level of the messenger RNA for the rat hepatic protein alpha 2u globulin

Abstract

Alpha 2u Globulin is a protein synthesized in the liver, secreted into the serum, and excreted in the urine of mature male rats. The effects of androgens and estrogens on the level of the messenger RNA coding for the male rat hepatic protein have been investigated. Castrated male rats have reduced levels of alpha 2u globulin in serum and liver cytosol, as measured by a radial immunodiffusion assay. The livers from these castrated males were found to contain similarly reduced levels of the mRNA coding for alpha 2u globulin, as measured in an mRNA-dependent wheat germ cell-free translational system. Administration of dihydrotestosterone to castrated males resulted in increased levels of alpha 2u globulin in liver and serum and this increase in the level of the protein following androgen administration was accompanied by a parallel increase in the functional level of alpha 2u globulin mRNA. Administration of estradiol-17 beta to intact male rats gradually diminishes the levels of alpha 2u globulin in liver and serum. The livers from these estrogen-treated males were found to contain alpha 2u globulin mRNA at similarly reduced levels. The time course of the disappearance of the alpha 2u globulin mRNA following estrogen treatment parallels the disappearance of the protein in liver cytosol and serum. These results indicate that sex steroids affect the synthesis of the hepatic protein alpha 2u globulin by acting pretranslationally, possibly at the level of transcription. Although the liver had not been considered a primary target tissue for sex hormones, these results indicate that sex steroids can affect certain hepatic functions in a manner consistent with the accepted model for the action of steroid hormones on their target tissues.