Effects of thyrotropin-releasing hormone and cyclo-histidine-proline on the homeothermic development of neonatal rats.

The effects of thyrotropin-releasing hormone (TRH) and its putative metabolite, cyclo-histidine-proline (cHP), on the homeothermic development of neonatal rats were studied. The daily intrathecal administration of 10(-11)-10(-9) moles of TRH during the second week of age produced a significant rise in body temperature by 3 weeks of age and was followed by a transient period of hypothermia. This effect, which could not be produced by an intraperitoneal injection of 10(-7) moles of TRH, was abolished by the simultaneous administration of 6-hydroxydopamine (6OHD). In contrast, intrathecally administered cHP decreased thermogenesis. During TRH treatment, brain norepinephrine (NE) and dopamine (DA) release was accelerated 2- to 4-fold. Two weeks after either TRH or cHP treatment, brain NE and DA were significantly reduced; adrenal NE in cHP-treated rats increased. The weight of the interscapular brown adipose tissue (BAT) was decreased by both cHP and 6OHD. At 3 weeks of age, [3H]guanosine diphosphate binding capacity in BAT mitochondria was reduced by 60% in TRH-treated rats and was associated with reduced mitochondrial levels of alpha-glycerophosphate dehydrogenase and liver cytochrome C reductase. These results indicate that TRH stimulates central NE release thereby enhancing thermogenesis, cHP decreases heat production, and TRH-induced hyperthermia is associated with changes in mitochondrial exothermic processes. The central TRH-cHP system may modulate the maturation of homeothermic mechanism in neonatal rats.