RESPONSE OF TRIIODOTHYRONINE-DEPENDENT ENZYME-ACTIVITIES TO INSULIN-LIKE GROWTH-FACTOR-I AND GROWTH-HORMONE IN CULTURED RAT HEPATOCYTES

Triiodothyronine (T-3) is involved in the regulation of the growth hor mone-insulin-like,growth factor I (GH-IGF-I) axis, In this study we in vestigated the effect of GH and IGF-I on the metabolic response of T-3 in target tissues by evaluating the activity of two T-3-dependent lin er enzymes: mitochondrial alpha-glycerophosphate dehydrogenase (alpha- GPD) and cytosolic malic enzyme (ME) in rat hepatocytes in primary cul ture, Growth hormone (35 nmol/l) as well as IGF-I (0.5 mu mol/l) reduc ed alpha-GPD and ME activities (p < 0.01) compared to the control grou p. Timecourse studies indicated that IGF-I (1.5 mu mol/l) significantl y decreased alpha-GPD and ME activities (p < 0.01) after 24h, 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 th is hypothesis, the effect of GH on the two enzyme activities was studi ed in the presence of anti-IGF-I antibodies, A gradual recovery of alp ha-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, T he maximal alpha-GPD and ME activities attained after the incubation o f the liver cells with 1 mu mol/l T-3 a concentration high enough to f ully saturate the nuclear T-3 receptors for 24h, were lowered signific antly by 1.0 mu mol/l IGF-I (p < 0.01), This finding suggests that the IGF-I effect might be independent of the saturation of the nuclear T- 3 receptors. In conclusion, in cultured rat hepatocytes, GH and IGF-I reduced the metabolic response of T-3 evaluated by two liner T-3 -depe ndent enzyme activities, The effect of GH was:as mediated at least in part by IGF-I.