Gamma-glutamyltransferase induction by dexamethasone in cytochrome P-450-depleted rat liver.
The effects of the cytochrome P-450 depletion by cobaltic protoporphyrin IX on the postnatal glucocorticoid-inducibility of the membrane-bound enzyme gamma-glutamyltransferase have been assessed in the rat liver. Dexamethasone-induced gamma-glutamyltransferase activity in 14-, 28- and 77-day-old rats was high, weak and absent, respectively, and inversely correlated with the physiological cytochrome P-450 activity. In the liver acinus, the enzyme was reexpressed by the zone 1 and zone 2 hepatocytes in suckling rats, substantially only by the zone 1-hepatocytes in just weaned rats. Following cytochrome P-450 depletion, gamma-glutamyltransferase induction by dexamethasone was more rapid, more intense and more extended in the liver acinus, occurring also in the zone 3 hepatocytes in suckling rats, in the zone 2 and a few zone 3 hepatocytes in just weaned rats. Further, the enzyme induction occurred also in adult rats in the zone 1 and in some zone 2 cells. This shows that cytochrome P-450 modulates the extent of hepatic gamma-glutamyltransferase induction by dexamethasone in postnatal rat-hepatocytes. The phenomenon may be consequent on hormone biotransformation changes caused by the cytochrome P-450 depletion.
Tongiani
R
R
Istituto di Patologia Generale, Università di Pisa, Scuola Medica, Italy.
Paolicchi
A
A
Chieli
E
E
D015660:7-Alkoxycoumarin O-Dealkylase / Q000032:analysis; D000367:Age Factors; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000172:deficiency*; D003907:Dexamethasone / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000502:physiology; D008099:Liver / Q000201:enzymology*; D008297:Male; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D005723:gamma-Glutamyltransferase / Q000096:biosynthesis* / Q000235:genetics
D011524:Protoporphyrins; C007095:cobaltiprotoporphyrin; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; D015660:7-Alkoxycoumarin O-Dealkylase; D005723:gamma-Glutamyltransferase