Effects of adrenergic drugs and monosodium glutamate on the development of sex-dependent cytochrome P450 system in male rat liver

Abstract

The effects of adrenergic drugs on the development of male-specific cytochrome P450 in the male rat liver were studied. Pups, castrated on Day 0, were given (icv) α-antagonist or β-agonist with or without testosterone propionate (sc.), and assayed on Day 65. Other pups were administered with (icv) adrenergic agonists or antagonists on Day 0 & 3 of life, castrated on Day 55, and assayed on Day 70. Neither α-antagonist nor β-agonist defeminized the EMDM activity in neonatally castrated rats. In the rats castrated on Day 55, β-antagonist and α₁-antagonist superdefeminized the EMDM activity. β-antagonist increased the total amount of P450 but α₁-antagonist did not. In addition, the Vmax of EMDM in β-antagonist-treated animals was increased; the Km was unchanged. Further, β-antagonist stimulated the activities of 16α-, 2α-, and 6β-testosterone hydroxylases in the superdefeminized rats. However, both β-antagonist and α₁-antagonist, given simultaneously, suppressed the superdefeminization of EMDM activity. -- The effect of monosodium glutamate (MSG) on the prepubertal development of male-specific cytochrome P450 in rat liver were also studied. Pups were treated on Day 1-9 with 2 or 4 mg/g MSG (sc), and on Day 35 the EMDM activities in 2 and 4 mg/g MSG-treated groups were the same as control values. However, MSG stimulated, dose-dependently, the EMDM activity on Day 65. In addition, Vmax of EMDM was elevated in MSG-treated group; the Km was unchanged. Finally, 4 mg/g MSG stimulated the activity of 6β- but not 16α/2α-testosterone hydroxylases.