EXPRESSION OF ADRENAL CYTOCHROMES-P-450 IN TESTOSTERONE-INDUCED HYPERTENSION

Chronic treatment of rats with the naturally occurring androgen, testosterone, leads to hypertension and cardiovascular disease. This effect is believed to be mediated through the adrenal gland and in particular by action on the steroid 11-beta-hydroxylase enzyme system. To study the possible mechanism of this effect, the enzyme system was examined at several time periods up to the time that hypertension develops. Rats were treated with testosterone (10 mg/day) for 3, 7, 21, and 42 days. Levels of cytochrome P-450(11-beta) enzyme and messenger RNA (mRNA) were determined as well as 11-beta-hydroxylase enzyme activity. A significant decrease in enzyme activity was observed after 3 days of treatment. This correlates with a profound decrease in the level of cytochrome P-450(11-beta) enzyme as determined by Western blot analysis. A large decrease in cytochrome P-450(11-beta) mRNA was also observed after 3 days of treatment. All three parameters remained low throughout the treatment period. The decrease in 11-beta-hydroxylase enzyme activity appears to result from a lower enzyme level brought about by decreased concentrations of mRNA transcripts.