Growth hormone releasing activity by intranasal administration of a synthetic hexapeptide (hexarelin)

Laron, Zvi; Frenkel, Jenny; Gil‐Ad, Lrit; Klinger, B.; Lubin, Ernesto; Wüthrich, Patrick; Boutignon, F.; Lengerts, Vincent; Deghenghi, Romano

doi:10.1111/j.1365-2265.1994.tb02589.x

Cited by 25 publications

(17 citation statements)

References 10 publications

(10 reference statements)

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“…The short-and long-term activity of the GHRPs, even when administered orally or intranasally (2,3,5,11), make them potentially superior to GHRH, whose use is restricted to injections (8).…”

Section: Discussionmentioning

confidence: 99%

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Desensitization from long-term intranasal treatment with hexarelin does not interfere with the biological effects of this growth hormone-releasing peptide in short children

Klinger

Silbergeld²,

Deghenghi³

et al. 1996

European Journal of Endocrinology

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A clinical, prospective experiment was carried out to determine whether long-term intranasal administration of the growth hormone-releasing peptide hexarelin (His-D-2-methyl-Trp-Ala-Trp-D-Phe -Lys-NH2) affects pituitary growth hormone secretion. Hexarelin (60 micrograms/kg t.i.d.) was administered to seven prepubertal constitutionally short children (mean age +/- SD = 7.6 +/- 2.4 years). Serum human growth hormone (hGH) response to an intranasal (20 micrograms/kg) and i.v. (1 mircogram/kg) bolus of hexarelin before, during and after 6-10 months of treatment was measured. The mean ( +/- SD) peak rise of hGH to the intranasal bolus before treatment was 70.6 +/- 28.2 mU/l. After 7 days of hexarelin treatment, mean peak values dropped to 34.1 +/- 15.7 mU/l (p < 0.002) and thereafter remained constant for 6 months of treatment at 37.5 +/- 10.3 mU/l (p < 0.03). The pretreatment peak to th i.v. hexarelin bolus was 84.8 +/- 52.5 mU/l, and at the end of the treatment period it was 19.8 +/- 10.9 mU/l (p < 0.05). Three months after stopping treatment the mean ( +/- SD) hGH response rose to 42.1 +/- 4.7 mU/l (p < 0.005). Growth velocity increased from 5.3 +/- 0.9 cm/year (before treatment) to 7.4 +/- 1.6 cm/year at 6-10 months of treatment (p < 0.005). In conclusion, teh partial suppression of pituitary hGH responsiveness to long-term intranasal hexarelin treatment, probably due to desensitization, does not affect the observed increase in growth velocity.

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“…The short-and long-term activity of the GHRPs, even when administered orally or intranasally (2,3,5,11), make them potentially superior to GHRH, whose use is restricted to injections (8).…”

Section: Discussionmentioning

confidence: 99%

“…Our group has demonstrated that hexarelin is a very potent stimulant of growth hormone (GH) release also in children (3,4), and long-term intranasal adminis¬ tration to short children induces an increase in serum IGF-I levels, anabolic metabolic changes and an acceleration of linear growth (5).…”

mentioning

confidence: 99%

Desensitization from long-term intranasal treatment with hexarelin does not interfere with the biological effects of this growth hormone-releasing peptide in short children

Klinger

Silbergeld²,

Deghenghi³

et al. 1996

European Journal of Endocrinology

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“…Intravenous ghrelin administration has not affected TSH blood levels in humans [36]. On the other hand, a well-known synthetic ghrelin analog, hexarelin, when applied intravenously or intranasally to GH-deficient patients, decreased TSH plasma levels, without affecting free T 4 and T 3 plasma levels in both tests [37]. The discrepancy between the studies may be explained by different experimental protocols, including variances in the duration of treatment (single or repetitive versus chronic treatment effects), route of administration (ICV versus intraperitoneal treatment effects), and/or applied dose.…”

Section: Discussionmentioning

confidence: 99%

Central Ghrelin Affects Pituitary-Thyroid Axis: Histomorphological and Hormonal Study in Rats

Šošić‐Jurjević

Stevanović²,

Milošević³

et al. 2008

Neuroendocrinology

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Body weight depends on the balance between energy intake and consumption. An interaction between ghrelin and thyroid function has been reported only in pathophysiological states. We examined whether intracerebroventricular (ICV) administration of ghrelin affects the structure and function of the pituitary-thyroid axis in young adult male rats. Ghrelin (0.3 nmol/5 μl PBS) or an equal volume of PBS were injected every 24 h into the lateral cerebral ventricle for 5 days. Two hours after the last treatment the animals were killed, their pituitaries and thyroids excised and prepared for further histological, immunohistochemical and morphometric investigation. Serum TSH levels were measured by RIA, while the total T₄ and T₃ levels were examined by ECLIA. Ghrelin treatment increased pituitary weight (p < 0.05) when compared to the controls, with no effect on the thyroid weight. Smaller, degranulated TSH-immunopositive cells were noticed within the pituitaries of ghrelin-treated animals; their cellular and nuclear volume as well as the relative volume density of thyrotrophs decreased (p < 0.05) in comparison to the control values. The level of serum TSH was reduced (p < 0.05). In the thyroid parenchyma of ghrelin-treated rats, an increased number of hypofunctioning follicles was noticed, characterized by flattened, weakly Tg-immunoreactive epithelium and colloid distension. The relative volume densities of the follicles and colloid increased (p < 0.05), while the thyroid index of activation rate and the serum level of total T₄ decreased (p < 0.05). In conclusion, centrally applied ghrelin modulated the immunohistomorphometric features of pituitary TSH cells and decreased the level of serum TSH, consequently changing thyroid morphology and function, by reducing the T₄ hormone level in the serum.

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“…The clinical efficacy and specificity of the GHRPs in elevating GH have been established (6) and more recently GH release in humans has been reported by using the GHRP-6 analog hexarelin (7,8). Furthermore, the nonpeptide L-692,429 (MK-0751) ( Fig.…”

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confidence: 99%

Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue.

Patchett

Nargund

Tata

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

314

201

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Growth hormone releasing activity by intranasal administration of a synthetic hexapeptide (hexarelin)

Cited by 25 publications

References 10 publications

Desensitization from long-term intranasal treatment with hexarelin does not interfere with the biological effects of this growth hormone-releasing peptide in short children

Desensitization from long-term intranasal treatment with hexarelin does not interfere with the biological effects of this growth hormone-releasing peptide in short children

Central Ghrelin Affects Pituitary-Thyroid Axis: Histomorphological and Hormonal Study in Rats

Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue.

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