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.
Gallant
S
S
Department of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York, Buffalo 14214.
Alfano
J
J
Charpin
M
M
Brownie
A C
AC
D000311:Adrenal Glands / Q000187:drug effects* / Q000201:enzymology; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis* / Q000235:genetics; D003900:Desoxycorticosterone / Q000378:metabolism; D005260:Female; D006973:Hypertension / Q000139:chemically induced / Q000201:enzymology*; D007527:Isoenzymes / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000494:pharmacology*
D007527:Isoenzymes; D012333:RNA, Messenger; D013739:Testosterone; D003900:Desoxycorticosterone; D000324:Adrenocorticotropic Hormone; D003577:Cytochrome P-450 Enzyme System