Long-term effects of thyrotropin-releasing hormone and histidyl-proline diketopiperazine on the maturation of homeothermia and mitochondrial enzyme activities in neonatal rats

Abstract

Abstract. To elucidate the mechanism by which TRH and its metabolite, histidyl-proline diketopiperazine (cyclo(His-Pro)), act on the maturation of homoiothermy, the chronic effects of intrathecal administration of the peptides on body temperature, serum thyroid hormone levels, and mitochondrial energy-producing enzyme activities were examined in neonatal rats. The two peptides or an equimolar mixture of both were injected intrathecally at a dose of 3, 6 and 9 nmol for 7 consecutive days during the 1st, 2nd or 3rd week of life, respectively. Control rats were treated with saline and they were sacrificed at 6 weeks of age. Although food and water intake were not decreased, body weight gain was slightly reduced in the rats treated with TRH or cyclo(His-Pro) during the 1st and 2nd week of life, whereas the mixturetreated rats showed normal weight gain. Body temperature at 25°C was not different in the TRH- and cyclo(HisPro)-treated groups, whereas after cold exposure (5°C for 3 h), the groups treated with TRH during the 1st and 2nd week of life had an impaired thermoregulation at 5 weeks of age. Serum T4 and T3 concentrations were similar in all groups, except in the rats treated with TRH during the 2nd week of life; their thyroid hormone levels were slightly reduced. The TRH treatment suppressed mitochondrial cytochrome c reductase and glucose-6-phosphatase activities, whereas cyclo(His-Pro) reduced cytochrome c reductase and malic enzyme activities. In contrast, α-glycerophosphate dehydrogenase was enhanced by both treatments. These results suggest that TRH and cyclo(His-Pro) modulate the central thermoregulatory mechanism and produce particular changes in the mitochondrial respiratory chains in peripheral thermogenic tissues.

Protein alterations induced by long‐term agonist treatment of HEK293 cells expressing thyrotropin‐releasing hormone receptor and G11α protein

“…These data indicate that TRH can not only affect the expression of mitochondrial proteins but also the production of mature proteins from appropriate precursors. In this context it can be worth to mention that chronic administration of TRH to neonatal rats altered activities of several mitochondrial enzymes [Miyamori et al, 1988].…”