Effects of streptozotocin-induced diabetes on rat liver sulfotransferase gene expression.
The effects of streptozotocin (STZ)-induced diabetes on rat hepatic hydroxysteroid sulfotransferase-a (HST-a) and aryl sulfotransferase IV (ASTIV) gene expression were characterized. Female Sprague-Dawley rats (aged approximately 55 days) were treated with increasing doses of STZ (65, 120, or 175 mg/kg ip) and killed 48 hr later. In some groups, diabetic rats were rendered normoglycemic with insulin before killing. STZ produced a dose-dependent increase in serum glucose levels and a dose-dependent suppression (of up to approximately 65%) of hepatic HST-a mRNA expression. Treatment with STZ (120 mg/kg ip) also significantly suppressed HST-a immunoreactive protein levels by approximately 31% relative to vehicle-treated controls. Reversal of STZ-induced diabetes with insulin significantly reduced the level of HST-a mRNA suppression associated with STZ treatment. The induction of diabetes with STZ (120 mg/kg ip) resulted in a approximately 63% suppression of HST-a mRNA expression, whereas insulin reversal of STZ-induced diabetes resulted in a approximately 34% suppression of HST-a mRNA levels. ASTIV mRNA levels displayed a significant level of suppression (approximately 35%) after treatment with STZ (65 mg/kg ip). However, unlike HST-a, treatment with higher doses of STZ (120 or 175 mg/kg) did not result in significant changes in ASTIV mRNA expression. These results suggest that, in mature female rats, the major hepatic sulfotransferase genes important to xenobiotic metabolism, HST-a and ASTIV, seem to be differentially regulated in response to STZ-induced diabetes. Moreover, negative regulation, possibly at the level of transcription, may be responsible for the changes in HST-a gene expression that accompany the development of STZ-induced diabetes.
Runge-Morris
M
M
Institute of Chemical Toxicology, Wayne State University, Detroit, MI 48201, USA.
Vento
C
C
D000818:Animals; D015239:Arylsulfotransferase / Q000096:biosynthesis / Q000235:genetics; D001345:Autoradiography; D015152:Blotting, Northern; D015153:Blotting, Western; D015342:DNA Probes; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015238:Sulfotransferases / Q000096:biosynthesis* / Q000235:genetics*
D015342:DNA Probes; D007328:Insulin; D015238:Sulfotransferases; D015239:Arylsulfotransferase; C044251:steroid sulfotransferase