Age-dependent regulation of the polymorphic forms of α(2u)-globulin

Hepatic synthesis of α(2m)-globulin in the male rat shows a gradual decline and ultimate loss during aging and senescene. Northern blot analysis with a cloned cDNA probe showed that the decrease in α(2u)-globulin synthesis during aging is associated wth a corresponding decrease in the concentration of its hepatic mRNA. By means of two-dimensional gel electrophoresis, α(2u)-globulin is resolved into a family of proteins. A monoclonal mouse antibody can identify at least five major isoelectric variants of α(2u)-globulin within the total protein synthesized by rat hepatocytes. These isoelectric variants are also present in the in vitro translation products of hepatic mRNA. An examination of the hepatic synthesis of the isoelectric variants of α(2u)-globulin during aging showed a differential regulation of the variant forms of this protein. Variant 2 (pI 6.1, the most prominent form) is the first to appear at puberty (40 days). The weakest member of the five major isoelectric forms (variant 4, pI 4.1) is the last to disappear at senescence. Although the overall decline in α(2u)-globulin synthesis during aging seems to be due to an age-dependent decrease in the androgen responsiveness of hepatocytes, it is postulated that the differential regulation of the isoelectric variants may represent changes at the level of the genes coding for this protein.