Abundance of cyclo (His-Pro)-like immunoreactivity in the brain of TRH-deficient mice.
Endocrinology
; 140(1): 538-41, 1999 Jan.
Article
em En
| MEDLINE
| ID: mdl-9886867
ABSTRACT
Cyclo(His-Pro) or CHP was initially discovered as a metabolite of thyrotropin-releasing hormone (TRH) resulting from the action of the enzyme Pyroglutamyl aminopeptidase. Physiologic and pharmacologic studies that followed this initial discovery provided indirect evidence that all CHP may not be derived from TRH. However, the recent availability of a TRH-deficient mouse has made it possible to reinvestigate whether CHP is derived from TRH. In the present study, we examined distribution of CHP and TRH in TRH-deficient mice. Northern blot analysis confirmed the absence of preproTRH mRNA in both the hypothalamus and the cortex of TRH-deficient mice. Brains from the wild-type and TRH-deficient mice were dissected into 7 regions, and TRH and CHP concentrations were determined by specific radioimmunoassay (RIA) in each region. Whereas TRH was identified in all regions of the wild-type brain, with the highest concentration in the hypothalamus, no detectable TRH was observed in any region in the TRH-deficient mice. While CHP-like immunoreactivity (CHP-LI) was present in all regions in the wild-type brain, its concentration was reduced by approximately 50% in the hypothalamus and cerebral cortex of TRH-deficient mice, with no change in other brain regions. Furthermore, the CHP-LI present in the brain of TRH-deficient mice was immunologically and chromatographically identical to synthetic CHP. These findings strongly suggest that a portion of the CHP in the brain is derived from sources other than TRH.
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Base de dados:
MEDLINE
Assunto principal:
Peptídeos Cíclicos
/
Piperazinas
/
Encéfalo
/
Inibidores da Captação de Neurotransmissores
/
Antioxidantes
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
1999
Tipo de documento:
Article