Találati lista | Tudóstér

001-es BibID:	BIBFORM033707
035-os BibID:	WOS:A1995RA15000032
Első szerző:	Izdebski, Jan
Cím:	Synthesis and biological evaluation of superactive agonists of growth hormone-releasing hormone / Jan Izdebski, Jacek Pinski, Judit E. Horvath, Gabor Halmos, Kate Groot, Andrew V. Schally
Dátum:	1995
ISSN:	0027-8424
Megjegyzések:	Analogs of the 29 amino acid sequence of human growth hormone-releasing hormone (hGH-RH) with agmatine (Agm) in position 29, desaminotyrosine (Dat) in position 1, norleucine (Nle) in position 27, and L-alpha-aminobutyric acid (Abu) in position 15 have been synthesized, and their biological activity was evaluated. Some peptides contained one or two residues of ornithine (Orn) instead of Lys in positions 12 and 21 and additional replacements in positions 8 and 28. All analogs were found to be more potent than hGH-RH-(1-29)-NH2 in the superfused rat pituitary cell system. In tests in vivo in rats after subcutaneous administration, the analogs JI-22, [Dat(1),Orn(12,21),Abu(15),Nle(27),Agm(29)]hGH-RH-(1-29); JI-34, [Dat(1),Orn(12,21),Abu(15),Nle(27),Asp(28),Agm(29)] hGH-RH-(1-29); JI-36, [Dat(1),Thr(8),Orn(12,21), Abu(15),Nle(27),Asp(28),Agm(29)]hGH-RH-(1-29); and JI-38, [Dat(1),Gln(8),Orn(12,21),Abu(15),Nle(27),Asp(28),Agm(29)] hGH-RH-(1-29) displayed a potency 44.6, 80.9, 95.8, and 71.4 times greater, respectively, than that of hGH-RH-(1-29)-NH2 at 15 min and 217.1, 89.7, 87.9, and 116.8 times greater at 30 min. After intravenous administration, JI-22, JI-36, and JI-38 were 3.2-3.8 times more potent than hGH-RH-(1-29)-NH2 at 5 min and 6.1-8.5 times more active at 15 min. All analogs were found to have higher binding affinities for GH-RH receptors on rat pituitary cells than hGH-RH-(1-29)-NH2. Because of high activity and greater stability, these analogs could be considered for therapy of patients with growth hormone deficiency.
Tárgyszavak:	Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban külföldön készült közlemény
Megjelenés:	Proceedings of The National Academy of Sciences of The United States of America. - 92 : 11 (1995), p. 4872-4876. -
További szerzők:	Pinski, Jacek Horváth Judit E. (New Orleans) Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Groot, Kate Schally, Andrew Victor
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Saját polcon:

001-es BibID:	BIBFORM033827
035-os BibID:	PMID:8875434 WOS:A1996VF15000001
Első szerző:	Kovács Magdolna
Cím:	Chronic administration of a new potent agonist of growth hormone- releasing hormone induces compensatory linear growth in growth hormone-deficient rats : mechanism of action / Magdolna Kovács, Gábor Halmos, Kate Groot, Jan Izdebski, Andrew V. Schally
Dátum:	1996
ISSN:	0028-3835
Megjegyzések:	To assess the efficacy of a potent agonist analog of GH-releasing hormone (GH-RH), [Dat1,Gln8,Orn12,21,Abu15,Nle27,Asp28,A gm29]hGH-RH(1-29) (JI-38), we investigated the effects of its chronic administration on growth responses in monosodium glutamate (MSG)-lesioned and normal young rats. Body weight (BW), body length (BL), tibia length (TIL), and tail length (TAL) were monitored. Basal serum GH concentrations, GH responses to bolus injections of GH-RH, pituitary GH and serum IGF-I concentrations were measured by RIA. Pituitary GH-RH receptor concentration and binding affinity was also evaluated after the treatment. Neonatal treatment with MSG resulted, as expected, in blunted growth and a decrease in serum and pituitary GH concentration and serum IGF-I levels. A reduction in GH-RH receptor concentration, associated with increased binding affinity of the GH-RH receptor was also found. Chronic administration of GH-RH agonist JI-38 in doses of 2 micrograms at 12-hour intervals for 2 weeks markedly increased the GH responsiveness to GH-RH and stimulated growth, with MSG-treated animals achieving the growth rate of normal controls. Acceleration of growth was associated with stimulated GH synthesis and IGF-I secretion, although basal serum GH levels did not change. Pituitary GH-RH receptor concentration and binding affinity were not significantly modified by the treatment. Treatment of normal young growing rats with agonist JI-38 did not further increase the normal growth acceleration in these rats, but stimulated the GH synthesis and augmented the GH secretory responsiveness. The treatment of MSG-lesioned rats with GH-RH agonist was generally more effective in female than in male animals, and in some cases masked the sex differences in growth rate. Our findings provide the first evidence that the blunted growth rate of the MSG-lesioned rats is associated with a decreased pituitary GH-RH receptor concentration. Our work demonstrates that administration of GH-RH agonist JI-38 is able to restore the normal growth rate of the GH-deficient rats by stimulating GH synthesis and IGF-I secretion.
Tárgyszavak:	Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban külföldön készült közlemény
Megjelenés:	Neuroendocrinology. - 64 : 3 (1996), p. 169-176. -
További szerzők:	Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Groot, Kate Izdebski, Jan Schally, Andrew Victor
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Saját polcon: