title: Response of triiodothyronine-dependent enzyme activities to insulin-like growth factor I and growth hormone in cultured rat hepatocytes.
abstract: Triiodothyronine (T3) is involved in the regulation of the growth hormone-insulin-like growth factor I (GH-IGF-I) axis. In this study we investigated the effect of GH and IGF-I on the metabolic response of T3 in target tissues by evaluating the activity of two T3-dependent liver enzymes: mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) and cytosolic malic enzyme (ME) in rat hepatocytes in primary culture. Growth hormone (35 nmol/l) as well as IGF-I (0.5 mumol/l) reduced alpha-GPD and ME activities (p < 0.01) compared to the control group. Timecourse studies indicated that IGF-I (1.5 mumol/l) significantly decreased alpha-GPD and ME activities (P < 0.01) after 24 h, whereas the effect of GH (35 nmol/l) was recorded only after 36 h (p < 0.01). This delayed effect of GH compared to IGF-I suggested the possibility that the effect of GH could be mediated by IGF-I synthesis. To test this hypothesis, the effect of GH on the two enzyme activities was studied in the presence of anti-IGF-I antibodies. A gradual recovery of alpha-GPD and ME activities (p < 0.01) was observed in the presence of GH (35 nmol/l) plus increasing concentrations of anti-IGF-I antiserum. The maximal alpha-GPD and ME activities attained after the incubation of the liver cells with 1 mumol/l T3, a concentration high enough to fully saturate the nuclear T3 receptors for 24 h, were lowered significantly by 1.0 mumol/l IGF-I (p < 0.01). This finding suggests that the IGF-I effect might be independent of the saturation of the nuclear T3 receptors. In conclusion, in cultured rat hepatocytes, GH and IGF-I reduced the metabolic response of T3 evaluated by two liver T3-dependent enzyme activities. The effect of GH was mediated at least in part by IGF-I.
authors.affiliation: Dpto Bioqúimica Clínica, Facultad de Ciencias Qúimicas, Universidad Nacional de Córdoba, Argentina.
authors.forename: C G
authors.initials: CG
authors.lastname: Pellizas
authors.forename: A H
authors.initials: AH
authors.lastname: Coleoni
authors.forename: A M
authors.initials: AM
authors.lastname: Cabanillas
authors.forename: A M
authors.initials: AM
authors.lastname: Masini-Repiso
authors.forename: M E
authors.initials: ME
authors.lastname: Costamagna
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003600:Cytosol / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism*; D013006:Growth Hormone / Q000494:pharmacology*; D007106:Immune Sera / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008291:Malate Dehydrogenase / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D014284:Triiodothyronine / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D007106:Immune Sera; D014284:Triiodothyronine; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D005993:Glycerolphosphate Dehydrogenase; D008291:Malate Dehydrogenase