AGE-DEPENDENT REVERSAL OF THE LOBULAR DISTRIBUTION OF ANDROGEN-INDUCIBLE ALPHA-2U-GLOBULIN AND ANDROGEN-REPRESSIBLE SMP-2 IN RAT-LIVER

Hepatocytes situated at pericentral and periportal zones of the liver lobule show differences in the expression of several liver-specific genes, such as androgen-inducible alpha-2u globulin and androgen-repressible senescence marker protein-2 (SMP-2). A marked temporal difference in the expression of these two androgen-regulated genes has also been observed. The liver of the pre-pubertal male rat is insensitive to androgen, and during this period hepatocytes synthesize only SMP-2. During young adult life (> 40 days), the liver becomes androgen sensitive and concomitant synthesis of alpha-2u globulin and repression of SMP-2 occur. In the senescent male rat (> 750 days), the liver again becomes androgen insensitive when the decline in alpha-2u globulin is accompanied by an increase in SMP-2 synthesis. In this article we present results to show a correlation between the temporal and spatial (intralobular) changes in the expression of the androgen-inducible alpha-2u globulin and the androgen-repressible SMP-2 in rat hepatocytes. Results indicate that the temporal changes in hepatic androgen sensitivity are dictated by the intralobular location of the hepatocytes. Hepatocytes located around the central vein (pericentral/perivenous) may benefit from a paracrine advantage for the expression of a subset of genes, including the gene for the androgen receptor.