67 The Role of Thyrotropin-releasing Hormone(TRH) and Histidyl-proline Diketopiperazine(HPD) in the Maturation of Thermogenesis in Growing Rats

Effects of TRH and its metabolite, histidyl-proline diketopi-perazine (HPD) on the maturation of thermogenesis were examined. Week old Wistar rats were administered 0.04, 0.4 or 4 nmoles of TRH or HPD intrathecally for 7 days. Half of the litters served as saline-treated controls. Body temperature upon cold exposure (5°C, 1-3 hrs) was measured weekly. On the 4th week of age, catecholamines in forebrain, midbrain, cerebellum, brain stem and adrenal glands were measured by HPLC with an EC detector. NADPH-dependent cytochrome C reductase(CCR) and ATPase activities were determined in liver mitochondria and microsomes. TRH showed a dose-dependent thermogenic effect while HPD potentiated hypothermia. This was associated with an elevated or reduced mitochondrial CCR activity in the TRH and HPD groups respectively. No significant differences were noted in either mitochondrial ATPase or microsomal CCR activity. Norepinephrine(NE) and dopamine in midbrain, cerebellum and brain stem were decreased in both groups but adrenal NE was increased in the HPD group. Dose-related changes were not apparent at 4 weeks of age. These results indicate that TRH and HPD exert antagonistic effects on thermogenesis and mitochondrial NADPH-dependent CCR activity and that these changes may be mediated by central and adrenal catecholamine release.