Pituitary component of the aromatic hydrocarbon-mediated expression of CYP2B and CYP2C11.
1. The aim was to determine if the ethylbenzene (EB)-mediated expression of CYP2B and CYP2C11 involved a hormonally controlled component. 2. The hypophysectomized (HX) and intact rats were treated with EB for 1 or 2 days, and the effects on specific CYP levels measured. 3. Differences were observed in the inducibility of CYP2B by EB in the HX rat when compared with intact controls. Whereas significant elevations of CYP2B-dependent activities and protein levels were observed after both 1 and 2 days of EB injection in intact controls, CYP2B levels were significantly elevated in the HX rat only after 2 days of hydrocarbon treatment. 4. Both CYP2C11-dependent activities and protein levels were decreased after EB administration to the intact rat. In contrast, CYP2C11 levels were unaffected by EB in the HX rat at any of the time points indicated. 5. CYP2C11 protein levels were unaffected by treatment with EB for 24 h in cultured hepatocytes, also supporting the hypothesis that hormones are involved in CYP2C11 expression. 6. This study indicates that pituitary input influences the EB-mediated changes in both CYP2B and CYP2C11. CYP2C11 is affected by EB administration in a manner similar to other xenobiotics such as phenobarbital. On the other hand, the smaller induction of CYP2B1/2 in response to EB differs from that observed with phenobarbital where HX augmented the response of the inducer.
Bergeron
R M
RM
Department of Pharmacology and Experimental Therapeutics, The Stanley S. Scott Cancer Center, Louisiana State University Medical Center, New Orleans 70112, USA.
Serron
S C
SC
Rinehart
J J
JJ
Cawley
G F
GF
Backes
W L
WL
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D001555:Benzene Derivatives / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000737:chemistry; D000072467:Cytochrome P450 Family 2; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007016:Hypophysectomy; D008099:Liver / Q000201:enzymology*; D019696:Peptidylprolyl Isomerase / Q000096:biosynthesis*; D010902:Pituitary Gland / Q000378:metabolism*; D051381:Rats; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000096:biosynthesis*
D001555:Benzene Derivatives; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C450279:CYP2C11 protein, rat; D000072467:Cytochrome P450 Family 2; D039181:Steroid 16-alpha-Hydroxylase; D019696:Peptidylprolyl Isomerase; C004912:ethylbenzene