Effect of the Orally Active Growth Hormone Secretagogue MK-677 on Somatic Growth in Rats
Yonsei Medical Journal
;
: 1174-1180, 2018.
Article
Dans Anglais
| WPRIM
| ID: wpr-718494
ABSTRACT
PURPOSE:
Growth hormone secretagogues (GHSs) possess the ability to release growth hormone (GH) in the body. This study aimed to investigate the effects of MK-677, an orally active GHS, on somatic growth in rats. MATERIALS ANDMETHODS:
The serum levels of GH were measured after oral administration of MK-677 to confirm GH stimulatory effects. Body weight, body length, tibia length, epiphyseal plate width, and serum levels of insulin-like growth factor (IGF)-I were measured after oral administration of 4 mg/kg of MK-677 for 6 weeks to investigate growth-promoting effects.RESULTS:
Oral administration of MK-677 at 4 mg/kg increased peak GH concentrations by 1.8-fold, compared to baseline. However, oral administration of MK-677 for 6 weeks did not increase body growth or serum levels of IGF-I. At 6 weeks after treatment, the GH response to MK-677 was abolished. Pituitary GH mRNA and hypothalamic GH-releasing hormone mRNA, and GH secretagogue receptor (GHSR) mRNA expression in the pituitary and hypothalamus did not differ between the control and treatment group. Somatostatin (SST) mRNA expression in the hypothalamus was markedly increased in the treatment group, whereas SST receptor (SSTR)-2 mRNA expression in the pituitary gland was decreased. Protein expression of hypothalamic GHSR, SST, and pituitary SSTR-2 showed patterns similar to those for mRNA expression.CONCLUSION:
Our results suggest that prolonged administration of MK-677 in rats does not promote growth despite the GH stimulatory effect of MK-677, which may be related to increased expression of SST in the hypothalamus. Further studies are needed to overcome the observed desensitization to GHS.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Hypophyse
/
Tibia
/
Poids
/
ARN messager
/
Facteur de croissance IGF-I
/
Somatostatine
/
Hormone de croissance
/
Administration par voie orale
/
Lame épiphysaire
/
Hypothalamus
Limites du sujet:
Animaux
langue:
Anglais
Texte intégral:
Yonsei Medical Journal
Année:
2018
Type:
Article
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