Developmental regulation of hepatic testosterone hydroxylases: simultaneous activation and repression of constitutively expressed cytochromes P450 in senescent rats.
The aging process is generally associated with marked decreases in the activities of numerous enzymes as well as lower levels of sex hormones such as testosterone. We therefore examined testosterone metabolism in liver microsomes from individual 3- and 24-month-old male rats. Although the old rats exhibited lower 16 alpha-, 6 beta-, and 2 alpha-hydroxylase activities than the young rats, the old rats had a higher 7 alpha-hydroxylase activity. Immunoquantitation of P450a, a known 7 alpha-hydroxylase, showed that the level of this protein was elevated in the old rats, and was correlated with 7 alpha-hydroxylase activity. The mRNA for P450a was measured with a cDNA probe and its level was fivefold higher in the old rats, whereas levels of mRNA coding for a 6 beta-hydroxylase P450 were markedly decreased. The increased expression of cytochrome P450a demonstrates that the observed common decrease in cytochrome P450-catalyzed activities with senescence is not a universal phenomenon. Thus, constitutive expression of specific cytochrome P450 genes is repressed or activated in senescent rats.
Robinson
R C
RC
Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Nagata
K
K
Gelboin
H V
HV
Rifkind
J
J
Gonzalez
F J
FJ
Friedman
F K
FK
D000375:Aging; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D008099:Liver / Q000254:growth & development*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C022724:testosterone 7-alpha-hydroxylase, hamster