Testosterone-Induced Hypertension in the Rat

Abstract

The effect of ACTH upon the inhibition of corticosteroidogenesis produced by treating rats with several synthetic adrogens has been evaluated. In experiments lasting about 2 weeks in which the simultaneous treatment with ACTH prevented the fall in adrenal weight due to the androgen therapy, corticosteroidogenesis measured in adrenal homogenates was still greatly reduced. Associated with the reduced production of corticosterone from progesterone there was a marked fall in the level of adrenal mitochondrial cytochrome P-450. The fall in cytochrome P-450 was not prevented by simultaneous treatment with ACTH. Treatment of rats with all 3 androgens, 17α-methylandrostenediol, 17α-methyltestosterone and 11β-hydroxy- 17α-methyltestosterone, brought about the decrease in cytochrome P-450 levels, whereas when metyrapone, a nonsteroidal competitive inhibitor of steroid 11β-hydroxylase, was given to rats for 6 weeks no change occurred in the level of adrenal mitochondrial cytochrome P-450. These data suggest that this property of the androgens is not necessarily related to their potential as inhibitors of steroid hydroxylases. (Endocrinology86: 1085, 1970)