Abstract

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.