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Titolo:
INHIBITION OF PITUITARY-ADRENAL SECRETION BY A CORTICOTROPIN-RELEASING HORMONE ANTAGONIST IN HUMANS
Autore:
BARAM TZ; MITCHELL WG; HALDEN E;
Indirizzi:
UNIV CALIF IRVINE,DEPT PEDIAT,MED SCI 1,ZOT 4475 IRVINE CA 92697 UNIV CALIF IRVINE,DEPT NEUROL IRVINE CA 92697 UNIV CALIF IRVINE,DEPT ANAT & NEUROBIOL IRVINE CA 92697 CHILDRENS HOSP LOS ANGELES,DIV NEUROL LOS ANGELES CA 90027 CHILDRENS HOSP LOS ANGELES,CLIN RES CTR LOS ANGELES CA 90027 UNIV SO CALIF LOS ANGELES CA 90027
Titolo Testata:
Molecular psychiatry
fascicolo: 4, volume: 1, anno: 1996,
pagine: 320 - 324
SICI:
1359-4184(1996)1:4<320:IOPSBA>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECEPTOR MESSENGER-RNA; RAT-BRAIN; STRESS; EXPRESSION; AXIS;
Keywords:
CRF; HYPOTHALAMO-PITUITARY-ADRENAL; RECEPTOR; NEUROPEPTIDE; ACTH; CORTISOL;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
24
Recensione:
Indirizzi per estratti:
Citazione:
T.Z. Baram et al., "INHIBITION OF PITUITARY-ADRENAL SECRETION BY A CORTICOTROPIN-RELEASING HORMONE ANTAGONIST IN HUMANS", Molecular psychiatry, 1(4), 1996, pp. 320-324

Abstract

Corticotropin releasing hormone (CRH) is the primary modulator of ACTH release from the pituitary, and a neuromodulator in limbic and autonomic brain regions. Dysfunction of CRH-mediated neurotransmission is emerging as a critical mechanism in several disorders. Therefore, modulation of CRH availability at receptor sites is a potentially powerful therapeutic tool. Inhibitory analogues of CRH have been tested in rodents and primates, but their safety and hormonal effects in humans are unknown. We administered a CRH-antagonist, alpha-helical-CRH-(9-41) tosix individuals. Each received two intravenous infusions: 50 mu g kg(-1) on day 1, and 100 mu g kg(-1) on the following morning. These doses block both endocrine and central effects of CRH in experimental animals. ACTH, cortisol, electrolytes, glucose and autonomic parameters were monitored in comparison with control values. Infusion of CRH antagonist did not alter heart rate, blood pressure, temperature or plasma electrolytes and glucose. Pre-infusion plasma ACTH levels averaged 26.8+/- 6.7 pg ml(-1) on day 1, and 29.0 +/- 5.8 pg ml(-1) on day 2. Post-infusion values were 11.8 +/- 2 and 11.5 +/- 2.4 pg ml(-1), significantly lower than pre-infusion levels. Plasma cortisol levels, which averaged 21.4 +/- 4 mu g dl(-1) on the first morning and 22.9 +/- 4.2 on the second, also decreased significantly after CRH antagonist infusions (to 14.0 +/- 2.9 mu g dl(-1) on day 1, and 13.9 +/- 3.0 mu g dl(-1) on day 2). Hormonal changes were transient, and circadian rhythm was not affected. Though not measured formally, euphoria, anxiety or somnolence were not observed. In conclusion, CRH antagonist administration to adults reduces hormonal secretion by pituitary corticotrophs, with resulting decrease in plasma ACTH and cortisol.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 13/07/20 alle ore 14:52:20