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Titolo:
Effects of the combined administration of hexarelin, a synthetic peptidyl GH secretagogue, and hCRH on ACTH, cortisol and GH secretion in patients with Cushing's disease
Autore:
Arvat, E; Ramunni, J; Giordano, R; Maccagno, B; Broglio, F; Benso, A; Deghenghi, R; Ghigo, E;
Indirizzi:
Univ Turin, Dipartimento Med Interna, Div Endocrinol, I-10124 Turin, ItalyUniv Turin Turin Italy I-10124 rna, Div Endocrinol, I-10124 Turin, Italy Europeptides, Argenteuil, France Europeptides Argenteuil FranceEuropeptides, Argenteuil, France
Titolo Testata:
JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION
fascicolo: 1, volume: 22, anno: 1999,
pagine: 23 - 28
SICI:
0391-4097(199901)22:1<23:EOTCAO>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
HORMONE-RELEASING PEPTIDE; GROWTH-HORMONE; PITUITARY; HEXAPEPTIDE; GHRP-6; ADRENOCORTICOTROPIN; L-692,585; RECEPTOR; INSULIN; ABSENCE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Ghigo, E Osped Molinette, Div Endocrinol, Cso Dogliotti 14, I-10126 Turin,Italy Osped Molinette Cso Dogliotti 14 Turin Italy I-10126 urin, Italy
Citazione:
E. Arvat et al., "Effects of the combined administration of hexarelin, a synthetic peptidyl GH secretagogue, and hCRH on ACTH, cortisol and GH secretion in patients with Cushing's disease", J ENDOC INV, 22(1), 1999, pp. 23-28

Abstract

Hexarelin (HEX) is a peptidyl GH secretagogue (GHS) which markedly stimulates GH release but, like other GHS, possesses also CNS-mediated ACTH- and cortisol-releasing activity. Interestingly, the stimulatory effect of HEX onACTH and cortisol release is exaggerated and higher than that of hCRH in patients with Gushing's disease (CD). To further clarify the mechanisms by which HEX stimulates the activity of hypothalamo-pituitary-adrenal (HPA) axis in man, in 6 patients with CD (6 women, 38-68 yr old) and in 7 control subjects (CS, 7 women, 22-29 yr old) we studied the effects of HEX (2.0 mu g/kg iv) and/or hCRH (2.0 mu g/kg iv) on ACTH and cortisol (F) secretion. TheGH responses to HEX alone and combined with hCRH were also studied in all subjects. Basal ACTH and F levels in CD were higher than in CS (66.3+/-5.1 vs 16.5+/-0.6 pg/ml and 217.8+/-18.5 vs 134.4+/-4.6 mu g/l, respectively; p<0.02). In CS, the ACTH and F responses to HEX, evaluated as Delta AUC (mean+/-SE: 128.7+/-39.2 pg*min/ml and 328.5+/-93.2 mu g*min/l, respectively) were lower, though not significantly, than those after hCRH (375.8+/-128.4 pg*min/ml and 1714.2+/-598.0 mu g*min/l, respectively), though the peak ACTHand F responses to both stimuli were similar. The co-administration of HEXand hCRH had an additive effect on both ACTH (1189.6+/-237.2 pg*min/ml) and F secretion (3452.9+/-648.6 mu g*min/l). In fact, the ACTH and F responses to HEX+hCRH were significantly higher (p<0.01) than those elicited by single stimuli. In GD, HEX induced ACTH and F responses (3603.8+/-970.7 pg*min/ml and 10955.9+/-6184.6 mu g*min/l, respectively) clearly higher (p<0.002)than those in GS. The HEX-induced ACTH and F responses in GD were higher, though not Significantly, than those recorded after hCRH (1432.7+/-793.5 pg*min/ml and 4832.7+/-2146.5 mu g*min/l, respectively). On the other hand, the hCRH-induced ACTH and F responses in CD were similar to those in CS. In GD, the coadministration of HEX and hCRH had an additive effect on ACTH (8035.7+/-1191.1 pg*min/ml) but not on F (10985.4+/-3900.8 mu g*min/l) secretion. In fact, the ACTH, but not the F response to HEX+hCRH was significantlyhigher (p<0.02) than that elicited by single stimuli. In conclusion, the present study demonstrates that in patients with Gushing's disease as well as in subjects control Hexarelin and hCRH have an additive effect on ACTH secretion. Considering that, at least in humans, differently from hCRH, GHS have no interaction with AVP, our present findings further agree with the hypothesis that the ACTH-releasing activity of GHS is, at least partially, independent of CRH-mediated mechanisms. (J. Endocrinol. Invest. 22: 23-28, 1999) (C)1999, Editrice Kurtis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 08/07/20 alle ore 23:42:09