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

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 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)

• Authors: C Miyamori, T Kato, E Imura, A Murata, T Sato, N Sakura, T Hashimoto
• Journal: Acta endocrinologica (Acta Endocrinol (Copenh)) Vol. 119 Issue 4 Pg. 575-81 (Dec 1988) ISSN: 0001-5598 [Print] Denmark
• PMID: 3144109 (Publication Type: Journal Article)

Chemical References

• Peptides, Cyclic
• Piperazines
• Thyroid Hormones
• NAD
• NADP
• Thyrotropin-Releasing Hormone
• histidyl-proline diketopiperazine

Topics

• Animals
• Body Temperature Regulation (drug effects)
• Injections, Spinal
• Mitochondria, Liver (enzymology)
• NAD (metabolism)
• NADP (metabolism)
• Peptides, Cyclic (pharmacology)
• Piperazines (pharmacology)
• Rats
• Rats, Inbred Strains
• Thyroid Hormones (blood)
• Thyrotropin-Releasing Hormone (pharmacology)
• Time Factors