Hormonal and developmental regulation of glycosylated α 2 u-globulin synthesis

Abstract

We have investigated the regulation of glycosylated α 2 u -globulin synthesis by examining the appearance of these molecules in the medium of primary monolayer cultures of hepatocytes. Hepatocytes were isolated from male and female rats of various ages, as well as from castrated or ovariectomized animals. α 2 u -Globulin was immunoprecipitated from the culture medium with rabbit antibody specific for α 2 u -globulin, and the dissociated precipitates were electrophoresed on sodium dodecyl sulfate-polyacrylamide gels. We found that prepubescent male and female rats synthesized only the high molecular weight glycosylated forms of α 2 u -globulin. Hepatocytes from 50-day-old intact and ovariectomized female rats, as well as from ovariectomized rats treated with 17β-estradiol, secreted only glycosylated α 2 u -globulin. Hepatocytes from castrated male rats treated with dihydrotestosterone in vivo synthesized the 20,000-dalton nonglycosylated form of α 2 u -globulin; the rate of glycosylated α 2 u -globulin synthesis was reduced in these cells. The rate of synthesis of glycosylated α 2 u -globulin by male rat hepatocytes declined concomitant with increases in the age of the rats, the level of serum testosterone, and the rate of synthesis of nonglycosylated α 2 u -globulin. Under our conditions, dexamethasone administration to castrated male rats or ovariectomized female rats in vivo did not alter the species of α 2 u -globulin that were synthesized subsequently by hepatocytes in vitro. Our results suggest that the synthesis of glycosylated α 2 u -globulin is regulated differently than the synthesis of the 20,000-dalton nonglycosylated form of α 2 u -globulin.