Hormonal regulation of male-specific rat hepatic cytochrome P-450g (P-450IIC13) by androgens and the pituitary.
The present study examines the hormonal regulation male-specific cytochrome P-450g (IIC13) and its mRNA. Neonatal gonadectomy of male rats abolished hepatic expression of P-450g and its mRNA in adulthood, while ovariectomy had little effect. Neonatal administration of testosterone to neonatally gonadectomized male or female rats partially masculinized expression of P-450g and its mRNA, and postpubertal administration of testosterone (testosterone capsules implanted at 5 weeks) completely masculinized their expression. However, castration of male rats at puberty (5 weeks) had no effect on P-450g or its mRNA at 10 weeks. Male-specific development of P-450g and P-450 M-1 (IIC11) mRNA were imprinted similarly by testosterone. However, hypophysectomy experiments demonstrated that the two male-specific forms of P-450 are regulated quite differently. Hypophysectomy of male rats decreased hepatic content of P-450 M-1 mRNA by approximately 50%, and intermittent injections of growth hormone completely restored this mRNA. In contrast, hypophysectomy of male rats increased P-450g and its mRNA by approximately 50%, while intermittent injections of growth hormone produced a slight decrease. Hypophysectomy of female rats increased P-450g and its mRNA to adult male levels, but produced only a small increase in P-450 M-1 mRNA. Continuous infusion of growth hormone into sham hypophysectomized male rats (to mimic the female growth hormone pattern) resulted in a complete loss of P-450g and its mRNA. These results indicate that the expression of P-450g is not dependent on the male pulsatile growth hormone pattern, but suggest instead that the continuous secretion of growth hormone suppresses P-450g in the female rat.
McClellan-Green
P D
PD
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Linko
P
P
Yeowell
H N
HN
Goldstein
J A
JA
D000818:Animals; D000831:Animals, Newborn; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics*; D004343:Drug Implants; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007016:Hypophysectomy; D008099:Liver / Q000254:growth & development*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D009919:Orchiectomy; D010052:Ovariectomy; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D051381:Rats; D011912:Rats, Inbred ACI; D012016:Reference Values; D012737:Sex Factors; D013739:Testosterone / Q000494:pharmacology*
D004343:Drug Implants; D012333:RNA, Messenger; D013739:Testosterone; D003577:Cytochrome P-450 Enzyme System