Pellizas CG, Coleoni AH, Cabanillas AM, Masini-Repiso AM, Costamagna ME. Response of triiodothyronine-dependent enzyme activities to insulin-like growth factor I and growth hormone in cultured cat hepatocytes. Eur J Endocrinol 1996:134:215–20. ISSN 0804–4643
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 α-glycerophosphate dehydrogenase (α-GPD) and cytosolic malic enzyme (ME) in rat hepatocytes in primary culture. Growth hormone (35 nmol/l) as well as IGF-I (0.5 μmol/l) reduced α-GPD and ME activities (p < 0.01) compared to the control group. Timecourse studies indicated that IGF-I 1.5 μmol/l) significantly decreased α-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 α-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 α-GPD and ME activities attained after the incubation of the liver cells with 1 μmol/l T3. a concentration high enough to fully saturate the nuclear T3 receptors for 24 h, were lowered significantly by 1.0 μmol/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.
Claudia G Pellizas, Dpto Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Códoba, Casilla de Correo 61, Sucursal 16, (5016) Córdoba, Argentina.
Autocrine secretion of insulin-like growth factor-I mediates growth hormone-stimulated DNA synthesis and proliferation in primary cultures of adult rat hepatocytes