By means of RNAase protection assay with an antisense cRNA probe, we have shown that the liver of the young adult male rat contains androgen receptor (AR) mRNA to a level of 4% compared to the prostate. Steady state levels of AR mRNA in the liver show both sex and age specificity. Compared to that of the male, the female liver contains a markedly reduced amount of AR mRNA. AR mRNA is almost undetectable in livers of prepubertal male (<35 days old) and senescent male (>750 days old) rats. Both prepubertal and senescent animals are relatively insensitive to the androgenic induction of α2u-globulin, a hepatic secretory protein. The age-dependent decline in hepatic androgen sensitivity and AR mRNA level can be delayed considerably by a 40% reduction in the dietary calorie intake. Analysis of poly (A)-containing RNA from two liver cell populations, hepatocytes and nonhepatocytes, revealed that only the hepatocytes that express α2u-globulin gene contain AR mRNA. From these results and our earlier observation of in vitro induction of α2u-globulin in isolated rat liver, we conclude 1) that androgen can act directly on hepatocytes to promote α2u-globulin synthesis; 2) that changes in the hepatic androgen sensitivity during maturation and aging are reflections of the age-dependent expression of the receptor gene; and 3) that retardation of the age-dependent loss of androgen sensitivity by calorie restriction is due to a concomitant delay in the decline of the hepatic AR mRNA level .
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