Enzymatic sulfation has been implicated to play a key role in a number of essential biological pathways including xenobiotic detoxication, carcinogen activation, and the regulation of intra-tissue hormone activity. In order to increase our understanding of the critical determinants governing the regulation of sulfotransferase gene expression, we investigated age-, gender-, and xenobiotic-related alterations in hydroxysteroid sulfotransferase-a or aryl sulfotransferase-IV gene expression. Northern blot and slot blot analyses showed that rat hepatic hydroxysteroid sulfotransferase-a mRNA expression was responsive to age- and gender-related signals. The results also suggested that the rat hepatic aryl sulfotransferase-IV and hydroxysteroid sulfotransferase-a genes are differentially regulated. Northern blot and reverse transcriptase polymerase chain reaction analyses demonstrated that hydroxysteroid sulfotransferase-a mRNA was expressed to a greater extent in female rat liver than in lung or kidney tissue. In addition, rat hepatic hydroxysteroid sulfotransferase-a gene expression in mature female rats, although not substantially altered in response to short-term fasting or high-dose dexamethasone treatment, was suppressed after treatment with the polycyclic aromatic hydrocarbon, 3-methylcholanthrene.