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Titolo:
Ablation of pituitary pro-opiomelanocortin (POMC) cells produces alterations in hypothalamic POMC mRNA levels and midbrain mu opioid receptor bindingin a conditional transgenic mouse model
Autore:
Zhou, Y; Unterwald, EM; Ho, A; LaForge, KS; Yuferov, VP; Kreuter, J; Sirianni, MJ; Allen, RG; Kreek, MJ;
Indirizzi:
Rockefeller Univ, Lab Biol Addict Dis, New York, NY 10021 USA Rockefeller Univ New York NY USA 10021 Addict Dis, New York, NY 10021 USA Temple Univ, Sch Med, Dept Pharmacol, Philadelphia, PA 19122 USA Temple Univ Philadelphia PA USA 19122 armacol, Philadelphia, PA 19122 USA Oregon Hlth Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR 97201 USA Oregon Hlth Sci Univ Portland OR USA 97201 oxicol, Portland, OR 97201 USA Oregon Hlth Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97201 USA Oregon Hlth Sci Univ Portland OR USA 97201 l Biol, Portland, OR 97201 USA
Titolo Testata:
JOURNAL OF NEUROENDOCRINOLOGY
fascicolo: 9, volume: 13, anno: 2001,
pagine: 808 - 817
SICI:
0953-8194(200109)13:9<808:AOPP(C>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
CORTICOTROPIN-RELEASING FACTOR; MESSENGER-RIBONUCLEIC-ACID; RAT ANTERIOR-PITUITARY; GLUCOCORTICOID REGULATION; BETA-ENDORPHIN; FACTOR CRF; PARAVENTRICULAR NUCLEUS; DIFFERENTIAL REGULATION; GENOMIC STRUCTURE; NERVOUS-SYSTEM;
Keywords:
POMC; CRH1 receptor; quantitative solution hybridization; quantitative autoradiography; conditional and targeted ablation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
55
Recensione:
Indirizzi per estratti:
Indirizzo: Zhou, Y Rockefeller Univ, Lab Biol Addict Dis, 1230 York Ave, New York, NY10021 USA Rockefeller Univ 1230 York Ave New York NY USA 10021 NY 10021 USA
Citazione:
Y. Zhou et al., "Ablation of pituitary pro-opiomelanocortin (POMC) cells produces alterations in hypothalamic POMC mRNA levels and midbrain mu opioid receptor bindingin a conditional transgenic mouse model", J NEUROENDO, 13(9), 2001, pp. 808-817

Abstract

The hypothalamic-pituitary-adrenal (HPA) axis is regulated by stress-related excitatory inputs, and various inhibitory and negative-feedback controlsby glucocorticoids and opioids, including pro-opiomelanocortin (POMC)-derived peptides. The role of POMC-derived peptides of pituitary origin in the modulation of brain POMC mRNA expression and opioid receptor binding was investigated using a line of transgenic mice that express a fusion gene composed of the pituitary expression-specific promoter region of the POMC gene driving the herpes simplex viral-1 thymidine kinase (TK). Male adult mice were treated with the antiherpes agent ganciclovir that selectively ablates cells expressing TK. Following treatment, POMC mRNA levels, measured by quantitative solution hybridization/RNase protection assays, were decreased by 48% in the pituitary of the TK+/+ mice, reflecting an expected loss of the pituitary corticotrope POMC cells. This treatment also significantly lowered pituitary beta -endorphin immunoreactivity content and plasma concentrations of corticosterone. In contrast, POMC mRNA levels were increased by 79% in the hypothalamus of the TK+/+ mice with pituitary POMC cell ablation. Binding of [H-3]DAMGO to mu opioid receptors, as measured by quantitative autoradiography, was significantly reduced in several brain regions including the central grey, median raphe and superficial grey layer of the superior colliculus. These regions are innervated by hypothalamic POMC neurones. No significant differences in binding to either kappa or delta opioid receptorswere found in the brain regions studied. These results suggest that POMC-derived peptides of pituitary origin may exert a tonic negative-feedback effect on hypothalamic POMC neurones. In turn, the downregulation of central mu opioid receptors in this model may be mediated through a mechanism related to hypothalamic POMC overexpression.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/01/20 alle ore 01:24:08