DIFFERENTIAL EXPRESSION OF HEPATIC ESTROGEN, PHENOL AND DEHYDROEPIANDROSTERONE SULFOTRANSFERASES IN GENETICALLY-OBESE DIABETIC (OB OB) MALEAND FEMALE MICE/

Sulphotransferases (STs) are a family of closely related enzymes playi ng a key role in regulation of the bioavailability and activity of imp ortant endogenous molecules such as steroid hormones. A relationship b etween the expression of steroid STs and the diabetic state has been d emonstrated in various laboratory animal models, and steroid sulphates such as dehydroepiandrosterane sulphate are known to have anti-diabet ic properties. In order to further our understanding of the molecular basis for the association of steroid hormone sulphation and diabetes, we have examined the expression of oestrogen, phenol and dehydroepiand rosterone (DHEA) STs in mice carrying the obesity mutation (ob), which in the homozygous state (ob/ob) produces mice which are obese and dia betic. Our data show that, in male mice, ST activities towards oestron e (E(1)), oestriol (E(3)), DHEA and the xenobiotic 1-naphthol are elev ated in ob/ob mice, whereas in female mice, only the oestrogen ST acti vities were elevated, with the DHEA and 1-naphthol ST activities reduc ed. Using antibodies directed against oestrogen ST, it was demonstrate d that the induction of E(1) and E(3) ST activity in ob/ob mice correl ated with the expression of an ST isoenzyme not constitutively express ed in control mouse liver.