Effects of somatostatin and testosterone on the hepatic monooxygenase system in castrated male rats.
In male rats exogenous growth hormone (GH) (5 mg . kg-1, twice a day for 7 days) reduced (p less than 0.05) the in vitro hepatic microsomal metabolism of ethylmorphine (EM) and hexobarbital (HB) by 59 and 33%; aniline (AN) metabolism and microsomal P-450 levels were unaltered but GH reduced (p less than 0.001) NADPH-cytochrome c reductase by 17%. GH had no effects in females. Castrated males receiving subreplacement doses of testosterone propionate (2 mg, three times weekly) were injected (280 micrograms . kg-1, three times a day for 4 days) with somatostatin (SS), an inhibitor of GH release: EM and HB metabolism was increased (p less than 0.01) 8 and 18%; AN hydroxylation and P-450 levels were unchanged; the reductase was elevated (p less than 0.01) 9%. In nonandrogenized castrates, SS effected greater changes: EM and HB metabolism was increased (p less than 0.01) 47 and 21%; AN metabolism and P-450 levels were unchanged; the reductase was increased (p less than 0.01) 27%. Conversely, SS had no effects in intact males at doses up to 1120 micrograms . kg-1, three times a day for 4 days. These data support the view that endogenous GH is a modulator of "feminized" drug metabolism in the adult male and that it is antagonized by testosterone. Attempts to inhibit drug metabolism with SS in the female were unsuccessful and may reflect the ineffectiveness of the preparations as they failed to inhibit growth in young rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Virgo
B B
BB
D000818:Animals; D002369:Castration; D003000:Clonidine / Q000494:pharmacology; D005260:Female; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors; D013004:Somatostatin / Q000494:pharmacology*; D013739:Testosterone / Q000494:pharmacology*
D013739:Testosterone; D013004:Somatostatin; D006899:Mixed Function Oxygenases; D003000:Clonidine