EFFECT OF SOME PEROXISOME PROLIFERATORS ON TRANSFORMING GROWTH FACTOR-BETA(1) GENE-EXPRESSION AND INSULIN-LIKE GROWTH-FACTOR II MANNOSE-6-PHOSPHATE RECEPTOR GENE-EXPRESSION IN RAT-LIVER/

Male Sprague-Dawley rats were given daily oral doses of either corn oi l (control), 80 mg/kg nafenopin (NAF), 50 mg/kg methylclofenapate (MCP ), 50 mg/kg Wy-14,643 (WY) or 250 mg/kg clofibric acid (CA) for 7 days . Ah four compounds increased relative liver weight and produced hepat ic peroxisome proliferation as assessed by induction of both peroxisom al (palmitoyl-CoA oxidation) and microsomal (lauric acid 12-hydroxylas e) fatty acid oxidising enzyme activities. RNA was extracted from live r samples and analysed for expression of transforming growth factor-be ta(1) (TGF-beta(1)) and the insulin-like growth factor II/mannose-6-ph osphate (IGFII/Man6P) receptor (which may be involved in transporting latent TGF-beta(1) into hepatocytes). TGF-beta(1) mRNA levels were inc reased to 151-178% of control by all four compounds, whereas NAF, MCP and WY, but not CA, increased IGFII/Man6P receptor mRNA levels to 195- 209% of control. The induction of TGF-beta(1) and IGFII/Man6P receptor expression by short term treatment with peroxisome proliferators may represent an adaptive response to limit the initial hyperplastic effec ts of such compounds.