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Titolo:
Skeletal growth acceleration with growth hormone secretagogues in transgenic growth retarded rats: Pattern-dependent effects and mechanisms of desensitization
Autore:
Wells, T; Houston, PA;
Indirizzi:
Cardiff Univ, Sch Biosci, Cardiff CF10 3US, S Glam, Wales Cardiff Univ Cardiff S Glam Wales CF10 3US ardiff CF10 3US, S Glam, Wales Natl Inst Med Res, Div Mol Neuroendocrinol, London NW7 1AA, England Natl Inst Med Res London England NW7 1AA crinol, London NW7 1AA, England
Titolo Testata:
JOURNAL OF NEUROENDOCRINOLOGY
fascicolo: 6, volume: 13, anno: 2001,
pagine: 496 - 504
SICI:
0953-8194(200106)13:6<496:SGAWGH>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
PITUITARY-ADRENAL AXIS; GH-RELEASING PEPTIDE-6; MESSENGER-RIBONUCLEIC-ACID; ARCUATE NUCLEUS; SYSTEMIC INJECTION; GENE-EXPRESSION; FOS EXPRESSION; FACTOR NEURONS; DW/DW RATS; RECEPTOR;
Keywords:
growth hormone; skeletal growth; growth hormone secretagogues; growth hormone secretagogue receptors; transgenic rats;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
53
Recensione:
Indirizzi per estratti:
Indirizzo: Wells, T Cardiff Univ, Sch Biosci, POB 911,Museum Ave, Cardiff CF10 3US, SGlam, Wales Cardiff Univ POB 911,Museum Ave Cardiff S Glam Wales CF10 3US les
Citazione:
T. Wells e P.A. Houston, "Skeletal growth acceleration with growth hormone secretagogues in transgenic growth retarded rats: Pattern-dependent effects and mechanisms of desensitization", J NEUROENDO, 13(6), 2001, pp. 496-504

Abstract

The transgenic growth retarded (Tgr) rat is the first genetic model of growth hormone (GH) deficiency whose growth can be accelerated with exogenous GH secretagogues (GHSs). In this study, we have demonstrated that GHS-receptor (GHS-R) mRNA expression in the arcuate nucleus of Tgr rats was not significantly different to that in wild-type littermates. We have confirmed that GHS-induced elevation in body weight gain was accompanied by accelerationof skeletal growth, and that the effects of the GHS, GHRP-6, were both dose- and pattern-dependent. The growth response with continuous infusion of GHRP-6 was transient, accompanied by suppression of GH and corticosterone responses to bolus injection of GHRP-6. This desensitization occurred withoutdownregulation of arcuate GHS-R mRNA expression, but was accompanied by elevated periventricular somatostatin mRNA expression. In contrast, pulsatile(3-hourly) infusion of GHRP-6 produced sustained growth and GH responses, which were accompanied by suppression of corticosterone responses and elevated arcuate GH-releasing factor (GRF) mRNA expression. Skeletal growth was further accelerated by coinfusion of GRF, but significant depletion of pituitary GH stores suggested that this growth rate may not be sustainable. These experiments confirm the importance of the Tgr rat for investigating the growth promoting potential of the GHSs in the context of GH-deficient dwarfism, and suggest that elevated somatostatin expression may mediate the suppression of the GRF-GH and hypothalamo-pituitary-adrenal axes following continuous GHRP-6 treatment.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/09/20 alle ore 04:24:36