Alterations in adenylate cyclase activity of the rat prostate gland

Abstract

1. 1. The ability of adenylate cyclase to respond to androgen deprivation and stimulation was investigated in the rat prostate gland. 2. 2. Enzyme activity decreased progressively after orchidectomy and, by 144 h, was only 37% of the values found in normal, mature rats. A single intramuscular dose (5 mg/100 g) of free testosterone to 120 h castrate rats restored adenylate cyclase activity of the prostate gland within 24 h. 3. 3. When free testosterone (5 mg/100g) was injected via the external jugular vein into 120 h castrate rats, a slight increase was noted after 2 h and by the 4 and 8 h, statistically significant increases in adenylate cyclase activity were recorded whether expressed per mg of tissue or per prostate. On the other hand, intravenous injection of dihydrotestosterone (5 mg/100 g), the active metabolite of testosterone, produced a significant increase (50%) in enzyme activity within 1 h and the observed stimulation was maintained up to 4 h following hormone treatment. 4. 4. The activity of cyclic AMP phosphodiesterase in the rat prostate was slightly inhibited 1 h after the intravenous injection of dihydrotestosterone. In contrast, testosterone treatment of castrate rats produced no significant change in prostate phosphodiesterase when compared to castrate control values. 5. 5. The testosterone-stimulated increases in adenylate cyclase activity of prostate glands in castrate rats were prevented by actinomycin D and cycloheximide as well as by a β-adrenergic blocking agent, propranolol. Cyproterone acetate, a potent anti-androgen, when given concurrently with testosterone, also inhibited the observed increase in enzyme activity. Moreover, administration of this anti-androgen, by itself, exerted a marked inhibitory effect on adenylate cyclase activity in prostates of 120 h castrate rats. 6. 6. The increase in prostatic adenylate cyclase was specific to male sex steroids since intravenous injection of estradiol-17β, progesterone or methyl prednisolone exerted little or no effect on enzyme activity. Results of the present study lend further support to the concept that stimulation of the cyclic AMP—adenylate cyclase system is an important feature of androgen action upon male accessory sex organs.