EFFECTS OF ANTIANDROGEN TREATMENT ON THE CATECHOLAMINE SYNTHETIC PATHWAY IN THE ADRENAL-MEDULLA OF SPONTANEOUSLY HYPERTENSIVE RATS

We investigated the effects of the antiandrogen flutamide on the activ ity of tyrosine hydroxylase, the levels of its encoding mRNA, and cate cholamine levels in the adrenal medulla of male spontaneously hyperten sive rats (SHR) and Wistar Kyoto rats (WKY). Flutamide (30 mg/kg) was administered subcutaneously daily (between 9 and 15 weeks of age). The systolic blood pressure of flutamide-treated SHR rats was lower than that of control SHR. Epinephrine and norepinephrine levels? tyrosine h ydroxylase activity, and the levels of encoding mRNA in the adrenal me dulla were significantly lower in flutamide-treated SHR rats than in p aired controls. Systolic blood pressure, epinephrine and norepinephrin e levels, tyrosine hydroxylase activity, and encoding mRNA in the adre nal medulla of WKY rats showed no significant differences between flut amide-treated and control groups. These findings suggested that flutam ide may have cardiovascular effects through alteration of the catechol amine synthetic pathway caused by removal of androgen receptor stimula tion on the expression of tyrosine hydroxylase in the adrenal medulla of male SHR rats.