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.
D002001:Adipose Tissue, Brown / Q000187:drug effects; D000311:Adrenal Glands / Q000187:drug effects; D000367:Age Factors; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D001921:Brain / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism; D006892:Hydroxydopamines / Q000494:pharmacology; D007036:Hypothermia, Induced; D007274:Injections, Intraperitoneal; D007278:Injections, Spinal; D008928:Mitochondria / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology*
D006892:Hydroxydopamines; D010456:Peptides, Cyclic; D010879:Piperazines; D006153:Guanosine Diphosphate; D013973:Thyrotropin-Releasing Hormone; C035273:N-(2-hydroxy-4-(isobutylcarbamoyl)butyryl)histidylprolinamide; D016627:Oxidopamine; C015924:histidyl-proline diketopiperazine; D004298:Dopamine; D009638:Norepinephrine