Long-term effects of thyrotropin-releasing hormone and histidyl-proline diketopiperazine on the maturation of homeothermia and mitochondrial enzyme activities in neonatal rats.
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 mixture-treated rats showed normal weight gain. Body temperature at 25 degrees C was not different in the TRH- and cyclo(His-Pro)-treated groups, whereas after cold exposure (5 degrees 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, alpha-glycerophosphate dehydrogenase was enhanced by both treatments.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D007278:Injections, Spinal; D008930:Mitochondria, Liver / Q000201:enzymology*; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013963:Thyroid Hormones / Q000097:blood; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*; D013997:Time Factors
D010456:Peptides, Cyclic; D010879:Piperazines; D013963:Thyroid Hormones; D009243:NAD; D009249:NADP; D013973:Thyrotropin-Releasing Hormone; C015924:histidyl-proline diketopiperazine