Aromatic hydrocarbon receptor expression and function in liver of hypophysectomized male rats.
The aromatic hydrocarbon receptor (AHR) acts as a ligand-activated transcription factor that mediates many of the biological responses to aromatic hydrocarbons, such as 3-methylcholanthrene (MC) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Some toxic effects are thought to be the result of AHR-mediated changes in the expression of endocrine-related genes, such as the estrogen receptor and genes involved in cell growth and differentiation. Since little is known about endocrine factors that regulate AHR expression and function, we evaluated the effect of hypophysectomy (hypx) on these parameters in the liver of male rats. Cytosolic AHR immunoreactive protein was reduced in hypx rats to 61% of levels in sham-operated rats. Sucrose density gradient analysis of cytosolic AHR radioligand binding using a saturating concentration of [3H]TCDD showed that ligand binding was reduced in hypx rats to 31% of sham levels. TCDD showed similar potency for transforming cytosolic AHR from hypx and sham rats to a DNA-binding form; however, maximal AHR DNA-binding was reduced in hypx rats to 57% of sham levels, although this did not achieve statistical significance. These changes observed at the protein level were not accompanied by a corresponding decrease in hypx rats of mRNA for AHR or the AHR nuclear translocator. Despite this change in AHR protein level, hypx rats were not compromised in hepatic cytochrome P450 1A1 induction following in vivo administration of MC. These data indicate that the AHR signaling pathway is intact in hypx rats and that a pituitary factor regulates hepatic AHR expression at the protein level.
Timsit
Yoav E
YE
Department of Pharmacology, Medical Sciences Building, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.
Chia
Frank Shih-Chang
FS
Bhathena
Anahita
A
Riddick
David S
DS
D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D015153:Blotting, Western; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004268:DNA-Binding Proteins; D004785:Environmental Pollutants / Q000633:toxicity; D004790:Enzyme Induction; D007016:Hypophysectomy; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008748:Methylcholanthrene / Q000633:toxicity; D008862:Microsomes, Liver / Q000378:metabolism; D010902:Pituitary Gland / Q000502:physiology* / Q000601:surgery; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity; D012313:RNA / Q000737:chemistry / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D018336:Receptors, Aryl Hydrocarbon / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
C497398:ARNT protein, rat; D004268:DNA-Binding Proteins; D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D008748:Methylcholanthrene; D012313:RNA; D019363:Cytochrome P-450 CYP1A1