Runge-Morris M, Vento C
Institute of Chemical Toxicology, Wayne State University, Detroit, MI 48201, USA.
Drug Metab Dispos. 1995 Apr;23(4):455-9.
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.
研究了链脲佐菌素（STZ）诱导的糖尿病对大鼠肝脏羟类固醇硫酸转移酶-a（HST-a）和芳基硫酸转移酶IV（ASTIV）基因表达的影响。对雌性Sprague-Dawley大鼠（约55日龄）腹腔注射递增剂量的STZ（65、120或175mg/kg），48小时后处死。在一些组中，糖尿病大鼠在处死前用胰岛素使其血糖正常。STZ导致血清葡萄糖水平呈剂量依赖性升高，并对肝脏HST-a mRNA表达产生剂量依赖性抑制（高达约65%）。相对于溶剂处理的对照组，腹腔注射STZ（120mg/kg）还显著抑制了HST-a免疫反应蛋白水平约31%。用胰岛素逆转STZ诱导的糖尿病显著降低了与STZ治疗相关的HST-a mRNA抑制水平。腹腔注射STZ（120mg/kg）诱导糖尿病导致HST-a mRNA表达抑制约63%，而用胰岛素逆转STZ诱导的糖尿病导致HST-a mRNA水平抑制约34%。腹腔注射STZ（65mg/kg）后，ASTIV mRNA水平显示出显著的抑制水平（约35%）。然而，与HST-a不同，用更高剂量的STZ（120或175mg/kg）处理并未导致ASTIV mRNA表达的显著变化。这些结果表明，在成熟雌性大鼠中，对异源物代谢重要的主要肝脏硫酸转移酶基因HST-a和ASTIV，似乎对STZ诱导的糖尿病有不同的调节反应。此外，负调节可能在转录水平，可能是导致STZ诱导糖尿病发展过程中HST-a基因表达变化的原因。
