RT Journal Article
SR Electronic
T1 Effects of streptozotocin-induced diabetes on rat liver sulfotransferase gene expression.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 455
OP 459
VO 23
IS 4
A1 M Runge-Morris
A1 C Vento
YR 1995
UL http://dmd.aspetjournals.org/content/23/4/455.abstract
AB 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.