PATHOLOGIC CHANGES IN SENSITIZED RATS TREATED WITH METHYLANDROSTENEDIOL AND WITH GROWTH HORMONE1

Abstract

The chronic administration of large doses of methylandro-stenediol (MAD) to the sensitized rat (unilateral nephrectomy and a 4% sodium chloride diet) causes hypertension, renal and cardiovascular pathology. In the present study MAD was administered to non-adrenalectomized, sensitized rats and to adrenalectomized-sensitized rats treated with adrenal cortex extract (ACE). The control groups did not receive MAD. Experiments 1 and 2 involved rats eating ad libitum. The dose of MAD was 10 mg/rat/day for 56 days; the adrenalectomized rats were each given 2 cc of ACE/day. The rats given MAD developed hypertension and renal and cardiovascular pathology in both the presence and absence of the adrenal glands. In Experiment 3, force-fed rats were given 20 mg of MAD/rat/day; the adrenalectomized rats were each given 1 cc of ACE/day. The duration of the experiment was 42 days. Hypertension and renal and cardiovascular changes were more severe in the non-adrenalectomized rats. It is concluded that the damaging effects of large doses of MAD can occur in the absence of the adrenal glands but that the presence of adrenal cortical hormones is required. In Experiment 4, a highly active preparation of growth hormone was given to sensitized rats eating ad libitum. There was an increase in body weight, food intake and all of the rats given GH developed a polydipsia, but the elevation in blood pressure and renal and cardiovascular changes were minimal.