Liver microsomal polypeptides from Fischer-344 rats affected by age, sex, and xenobiotic induction

Abstract

In order to investigate age and sex as determinants of hepatic cytochromes P-450, the polypeptide compositions of liver smooth microsomes from Fischer-344 rats were examined using two-dimensional gel electrophoresis ( G. P. Vlasuk and F. G. Walz, Jr. (1980) Anal. Biochem. 105, 112). The effects of phenobarbital and 3-methylcholanthrene treatments were investigated using sexually immature (1 month), young adult (3 months), middle aged (12 months), and senescent (26 months) animals of both sexes. The appearance of five major microsomal polypeptides characterized sexual maturation in males. The only qualitative difference in the patterns of xenobiotic-induced polypeptides were found for young adult and middle-aged males where cytochrome P-450a ( D. Ryan, P. E. Thomas, D. Korzeniowski, and W. Levin (1979) J. Biol. Chem. 254, 1365) was not induced by phenobarbital. A number of major microsomal polypeptides which might represent unidentified forms of cytochrome P-450 in untreated males and females were markedly decreased in a specific manner as a result of phenobarbital and/or 3-methylcholanthrene treatments. Microsomes from females of all ages tested and immature males were essentially indistinguishable on the basis of their total cytochrome P-450 contents and polypeptide patterns. Untreated senescent males were characterized by a reversion of their microsomal polypeptide patterns and total cytochrome P-450 contents to those for females and sexually immature males. In addition, phenobarbital-induced levels of total cytochrome P-450 for senescent males were the lowest observed for all of the groups tested even though their pattern of induced polypeptides was qualitatively the same as that for females.