Role of glucose utilization in the restoration of hypophysectomy-induced hepatic cytochrome P450 2E1 by growth hormone in rats

Growth hormone and insulin are the primary determinants for cytochrome P450 2E1 (CYP2E1) expression. The role of glucose on the induction of CYP2E1 by hypophysectomy and on the restorative effect by growth hormone was investi gated in the rat liver. Western and Northern blot analyses revealed that hy pophysectomy induced CYP2E1 by 5-fold at 1-4 weeks, relative to control, wi th a concomitant increase in CYP2E1 mRNA. Hypophysectomized rats (HXR) show ed a 20% reduction in the plasma glucose level. Hypophysectomy-induced incr ease in the CYP2E1 mRNA was completely abolished by glucose feeding in drin king water (10%) for 7 days. Treatment of HXR with hGH (2 I.U./kg, twice a day, for 7 days) inhibited the increases in CYP2E1 protein and mRNA levels with restoration of the plasma glucose level. In contrast to the effect of human growth hormone (hGH) on CYP2E1 in HXR with free access to foods. CYP2 E1 expression failed to be restored by hGH in starving HXR, However, glucos e feeding of starving HXR abolished the induction of CYPE1. Effects of hypo physectomy and hGH treatment were studied in streptozotocin-induced diabeti c rats. Insulin, but not hGH, prevented an increase in CYP2E1 mRNA in diabe tic rats. The hepatic CYP2E1 induction in hypophysectomized diabetic mts wa s inhibited by hGH treatment, indicating that the hGH effect on CYP2E1 expr ession did not involve insulin production. These results provide evidence t hat the induction of hepatic CYP2E1 by hypophysectomy may result from reduc ed glucose utilization, and that the effect of hGH on CYP2E1 expression may be mediated with enhanced glucose utilization, but not with insulin produc tion. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.