Biomedical subjects

R Deghenghi

Publications and source records attributed to R Deghenghi.

At least 109 records · Page 6Linked to original sources

PubMed1996

Somatotrope responsiveness to Hexarelin, a synthetic hexapeptide, is refractory to the inhibitory effect of glucose in obesity.

Both spontaneous and stimulated growth hormone (GH) secretion is reduced in obesity, in which state insensitivity to the inhibitory effect of hyperglycemia also has been reported. To further investigate this point, in eight male obese (OB) patients (27-49 years old; body mass index = 39.5 +/- 1.7 kg/m2) we studied the effect of oral glucose load (100 g) on the GH response to Hexarelin (HEX, 2 micrograms/kg iv), a synthetic hexapeptide belonging to the GH-releasing peptide family, which has been reported to be able to induce a marked GH rise even in obese patients. As a control group, six male age-matched normal subjects (NS) were studied (26-35 years old; body mass index = 22.3 +/- 1.5 kg/m2). In all subjects the GH response to growth hormone-releasing hormone (GHRH, 1 microgram/kg iv) was also studied. Basal GH and insulin-like growth factor I (IGF-I) levels in OB and NS were similar (0.3 +/- 0.1 vs 0.5 +/- 1.0 microgram/l and 166.7 +/- 12.3 vs 145.4 +/- 6.9 micrograms/l, respectively). Hexarelin induced a clear GH rise in OB (peak: 20.0 +/- 2.9 micrograms/l; AUC: 1193.0 +/- 213.7 micrograms.l-1.120 min-1) but this response was clearly lower (p < 0.0002) than that observed in NS (62.6 +/- 7.3 micrograms/l, 4587.5 +/- 614.9 micrograms.l-1.120 min-1). The GHRH-induced GH rise was lower (p < 0.002) in OB (4.4 +/- 1.2 micrograms/l, 331.0 +/- 95.9 micrograms.l-1.120 min-1) than that in NS (20.2 +/- 1.9 micrograms/l, 1281.0 +/- 157.5 micrograms.l-1 .120 min-1) and both were lower (p < 0.05) than those induced by HEX. In NS, glucose significantly blunted the GH response to HEX (38.4 +/- 7.2 micrograms/l, 2236.5 +/- 514.8 micrograms.l-1.120 min-1, p < 0.05) but failed to modify it in OB (19.4 +/- 2.7 micrograms/l, 934.5 +/- 151.3 micrograms.l-1. 120 min-1). Plasma glucose peaks after oral glucose load in OB and NS were similar (164.5 +/- 9.7 vs 145.8 +/- 4.6 mg/dl). In conclusion, the present data demonstrate that, in contrast to normal subjects, in obese patients HEX has a reduced GH-releasing effect that is not inhibited by glucose. In OB patients as well as in normal subjects HEX releases more GH than GHRH. These findings strengthen the evidence that GH secretion in obesity is refractory either to stimulatory inputs or to the inhibitory effect of hyperglycemia.

Administration, Oral↗

PubMed1995

Metabolic modulation of the growth hormone-releasing activity of hexarelin in man.

Hexarelin (His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2) is a new potent synthetic growth hormone (GH)-releasing hexapeptide. The mechanism of action of hexarelin in man has never been evaluated. Hexarelin may act directly on specific pituitary receptors and indirectly on the hypothalamus. To elucidate its mechanism of action in man, we studied the interaction of hexarelin with glucose and free fatty acids (FFA), two metabolic factors known to inhibit both basal and GH-releasing hormone (GHRH) stimulated GH secretion. Glucose is thought to inhibit GH secretion via stimulation of endogenous somatostatin release, whereas FFA could also act directly on somatotrope cells. Therefore, we investigated the effect of oral glucose (100 g) and lipid-heparin infusion (250 mL of a 10% lipid solution + 2,500 U heparin) on the GH response to a maximal dose (2 micrograms/kg intravenously [IV]) of hexarelin or GHRH in six normal men. Hexarelin elicited a clear-cut GH response (mean +/- SEM; peak, 62.6 +/- 8.0 micrograms/L) that was higher (P < .01) than that observed after GHRH (peak, 19.8 +/- 2.4 micrograms/L). Although similar increases in plasma glucose were observed with the two peptides, oral glucose almost abolished the GH response to GHRH (peak, 5.6 +/- 0.9 micrograms/L, P < .01) while only blunting the somatotrope response to hexarelin (peak, 38.4 +/- 7.9 micrograms/L, P < .05). Similarly, lipid-heparin infusion nearly abolished the GH response to GHRH (peak, 4.9 +/- 1.0 micrograms/L, P < .01) while only blunting the somatotrope response to hexarelin (peak, 34.2 +/- 4.5 micrograms/L, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1995

Synthesis and properties of novel block copolymers containing poly(lactic-glycolic acid) and poly(ethyleneglycol) segments.

A synthetic process for obtaining high-molecular-weight block copolymers containing poly(lactic-glycolic acid) and poly(ethylene glycol) segments has been established. This process involves the reaction of poly(ethylene glycols) with phosgene, followed by polycondensation of the resulting alpha, omega-bis(chloroformates) with poly(lactic-glycolic acid) oligomers. The copolymers have been characterized for their molecular weight, solubility properties, water absorption and preliminarily thermal behaviour. All evidence points to the conclusion that the process described is a general one, enabling biodegradable polymers to be obtained tailor-made according to specific requirements.

Biocompatible Materials↗

PubMed1995

Hexarelin, a potent GHRP analogue: interactions with GHRH and clonidine in young and aged dogs.

The GH-releasing activity of hexarelin was evaluated in unanesthetized young and aged dogs. Hexarelin (15.6-250 micrograms/kg, i.v.) significantly stimulated GH secretion in a dose-dependent fashion in dogs of both age groups. The ability of hexarelin to potentiate the GH-releasing effect of GHRH (2 micrograms/kg, i.v) and clonidine (4 micrograms/kg, i.v.) was then tested. Hexarelin strikingly potentiated the effect of GHRH both in young and aged dogs, whereas it potentiated the effect of clonidine in young dogs only. Because clonidine acts on the hypothalamus to release GHRH, its failure to synergize with hexarelin in aged dogs is likely due to an age-related impairment of GHRH-secreting neurons.

Age Factors↗

PubMed1995

Radioimmunoassay for hexarelin, a peptidic growth hormone secretagogue, and its pharmacokinetic studies.

A radioimmunoassay (RIA) method for hexarelin, a peptidic growth hormone secretagogue, has been developed and applied to pharmacokinetic studies in dogs following an IV dose of 1 microgram/kg, and three SC doses of 1, 10, and 100 micrograms/kg. The sensitivity of the assay was determined to be 1.34 fmol/assay. Cross-reactivity of the antiserum with nine hexarelin analogues was less than 1% upon modification of positions 3, 4, or 5 of the peptide. No apparent cross-reaction with endogenous hexarelin metabolites were observed. Intra- and interassay coefficients of variation were less than 3% and 4%, respectively. Intravenous bolus pharmacokinetics of hexarelin displayed a high terminal half-life of 120 min, a fractional plasma clearance of 4.28 ml/min/kg, and a volume of distribution at steady state of 387.7 ml/kg. Following SC administration of hexarelin, despite the increase in dose administered, both clearance (3.93-5.17 ml/min/kg) and volume of distribution (316-544 ml/kg) parameters remained constant over the dose range studied.

Amino Acid Sequence↗

PubMed1995

Hexarelin, a novel GHRP-6 analog, counteracts the inhibitory effect of hydrocortisone on growth hormone secretion in acromegaly.

Hexarelin (His-D-2-Methyl-Trp-Ala-Trp-D-Phe-Lys-NH2) is a GHRP-6 analog with the substitution of D-tryptophan with its 2-methyl derivative. The aim of our study was to ascertain whether hexarelin was able to counteract the glucocorticoid-mediated increase in hypothalamic somatostatin tone and consequent inhibition on serum GH levels in acromegalic patients. Ten patients (5 males, 5 females; age range 27-71 years; BMI range 23.3-35 kg/m2) with active acromegaly underwent: 1) hydrocortisone alone: a bolus iv injection of 100 mg hydrocortisone succinate in 2 mL saline, at time -60 followed by a 120 min iv infusion of 250 mg hydrocortisone succinate in 250 mL saline, from -60 to 60 min; 2) hexarelin+hydrocortisone: a bolus iv injection of hexarelin 100 micrograms, 60 min after initiation of a 2-hour hydrocortisone infusion; 3) hexarelin alone: a bolus iv injection of hexarelin at time 0, 60 min after initiation of a 2-hour saline infusion. The mean GH peak, expressed as percent change with respect to baseline level (mean of -75 and -60 minute samples), after hexarelin (1750 +/- 1157%) did not differ significantly with respect to that observed after hexarelin+hydrocortisone (1120 +/- 770%). After hydrocortisone alone the patients showed a mean decrease in GH levels as compared to baseline levels, of 47 +/- 7%. Our data show that the GH response to hexarelin in acromegaly is resistant to the inhibitor action of an acute and sustained elevation of serum cortisol levels. That hexarelin counteracts the glucocorticoid-mediated inhibition of GH secretion supports the hypothesis of an hexarelin-induced decrease in endogenous somatostatin tone.

Acromegaly↗

PubMed1995

Intranasal administration of the GHRP hexarelin accelerates growth in short children.

OBJECTIVE: Hexarelin is a recently synthesized small growth hormone releasing peptide (GHRP) (His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys- NH2). It is active by intravenous, oral and intranasal administration in animals and man. The aim of this study was to find out whether long-term administration of this peptide would promote growth in short children. DESIGN AND PATIENTS: Intranasal hexarelin was administered in a dose of 60 micrograms/kg thrice daily to 8 prepubertal short children aged 4-11.6 years for periods of up to 8 months. RESULTS: Hexarelin treatment stimulated insulin-like growth factor-I (IGF-I) secretion raising the level from 10.4 +/- 3.9 (SD) to 14.1 +/- 4.6 nmol/l (P < 0.004). The rise in IGF-I led to a significant increase in the mean (+/- SD) linear growth velocity from 5.3 +/- 0.8 to 8.3 +/- 1.7 cm/year (P < 0.0001). There was also a significant decrease in skinfold thickness despite increase in body weight and an increase in head circumference. Additional findings were a rise in serum phosphate from 1.5 +/- 0.1 to 1.8 +/- 0.1 mmol/l (P < 0.004) and of alkaline phosphatase from 219 +/- 74 to 261 +/- 75 U/l (P < 0.05). CONCLUSIONS: The long-term GH/IGF-I stimulating, anabolic and growth promoting effects achieved by intranasal administration of this hexapeptide, seemingly without undesirable side-effects, suggests clinical potential for this new class of drugs.

Administration, Intranasal↗

PubMed1995

Mechanism of action of hexarelin and GHRP-6: analysis of the involvement of GHRH and somatostatin in the rat.

We have recently reported oral and parenteral bioactivity for a new GH-releasing peptide, hexarelin. In the present study, we have examined the neuroendocrine mechanism by which hexarelin and GHRP-6, two GH-releasing peptides, mediate their actions. Although previous studies have looked at the role of growth hormone-releasing hormone (GHRH) and somatostatin in regulating the action of GHRP-6 in culture and in stressed animals, our study looked at the role of both somatostatin and GHRH in regulating the action of hexarelin as well as GHRP-6 in conscious and freely-moving, nonstressed rats. Adult male rats, prepared with indwelling jugular catheters, were pretreated i.v. with either control antiserum (CTLas), growth hormone-releasing hormone antiserum (GHRHas), somatostatin antiserum (SSas), or both GHRHas and SSas. Animals were then treated i.v. with 25 micrograms/kg of either hexarelin or GHRP-6 4 h after i.v. antisera pretreatment. Blood samples were collected every 20 min for the 3 h prior to peptide treatment and at 5, 10, 15, 20, 40 and 60 min following hexarelin or GHRP-6 injection. The peak plasma GH responses in rats pretreated with CTLas were 552 +/- 125 ng/ml following hexarelin administration and 386 +/- 132 ng/ml following GHRP-6 administration. Rats pretreated with SSas exhibited peak GH responses following hexarelin or GHRP-6 of 702 +/- 115 and 312 +/- 42 ng/ml, respectively. These plasma GH responses were similar to those observed in the CTLas-pretreated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1995

Modulation of growth hormone-releasing activity of hexarelin in man.

Hexarelin (His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2) is a new synthetic growth hormone (GH)-releasing hexapeptide. The mechanism of action of hexarelin in man is not fully elucidated. As for other GH-releasing peptides, an action on both the pituitary gland and the hypothalamus has been hypothesized. In the present study, we evaluated the modulation of GH-releasing activity of hexarelin in man. In a first experiment conducted on 6 healthy male volunteers, we studied the interaction of the maximally effective intravenous dose of hexarelin (2 micrograms/kg i.v.) with GH-releasing hormone (GHRH, 2 micrograms/kg i.v.) and somatostatin (2 micrograms/kg/h i.v.). In a second experiment involving another 6 male subjects, we evaluated the interaction of hexarelin with neuroactive substances, such as pirenzepine (0.6 mg/kg i.v.), pyridostigmine (120 mg p.o.) and arginine (0.5 g/kg i.v.), thought to modulate endogenous somatostatin secretion. Hexarelin induced a higher increase in GH levels as compared to GHRH (integrated output calculated as area under the curve AUC0-120 4,693 +/- 691 vs. 1,494 +/- 102 micrograms.min/l, p < 0.01). Coadministration of hexarelin and GHRH produced a higher GH response than hexarelin alone (AUC0-120 7,395 +/- 450 micrograms.min/l, p < 0.05). Somatostatin abolished the GH response to GHRH (AUC0-120 363 +/- 89 micrograms.min/l, p < 0.01), while it only blunted that to hexarelin (AUC0-120 1,314 +/- 297 micrograms.min/l, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Somatotropic dysregulation in old mammals.

In old mammals, including humans, the spontaneous growth hormone (GH) secretory pattern is markedly reduced resulting in lower amounts of GH released over 24 h, and the GH response to administration of GH-releasing hormone (GHRH) is reduced. In agreement with these in vivo findings, an impaired responsiveness to GHRH is evident in the pituitary of old male and female rats in vitro, and this is linked with a diminished stimulation of adenylate cyclase by GHRH. The poor GH responsiveness to GHRH in old mammals, which in the rat is coupled to a defective number of GHRH receptors in the somatotrophs, is likely due to a primary deficiency of GHRH availability, as implied by the diminished GHRH immunoreactivity and gene expression in and GHRH release from the hypothalamus of old rats. Attempts have been made to stimulate the sluggish somatotrophic function in elderly humans and dogs using GHRH; in either species positive results were obtained though, overall, it would seem that the GHRH hypofunction does not entirely account for the GH hyposecretory state during ageing. Concerning somatostatin, although the expression of this peptide decreases with age in the rat hypothalamus, secretion and activity of this hormone is increased, resulting in an altered relationship between GHRH and somatostatin gene expression and secretion. It is likely that defects, especially in catecholaminergic and cholinergic neurons, are instrumental in altering specific peptidergic neurons. Reportedly, catecholamines induce GH release by stimulating GHRH neurons and inhibiting somatostatin-releasing neurons; acetylcholine stimulates GH release via muscarinic receptors, in this way inhibiting the action of somatostatin neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1995

Growth hormone-releasing activity of hexarelin, a new synthetic hexapeptide, before and during puberty.

The objective of this study was to verify the GH-releasing activity of a synthetic hexapeptide, hexarelin (HEX), before and during puberty. Ninety-six children (54 boys and 42 girls, aged 4.1-17.4 yr) were studied. Fifty-two of the children were prepubertal, and the other 44 were in pubertal stage II-IV. The GH response to 2 micrograms/kg HEX, iv (n = 56), was higher (P < 0.001) than that induced by 1 microgram/kg GHRH, iv (n = 33). The iv dose of 2.0 micrograms/kg HEX induced a greater GH increase (P < 0.02) than the 1.0 microgram/kg dose. The GH-releasing effect of 10 mg HEX, orally, was greater (P < 0.03) than that of 1.0 microgram/kg GHRH, iv (n = 7). The iv dose of 2 micrograms/kg HEX elicited an increase in GH levels that was higher in pubertal children than in prepubertal children (77.5 +/- 8.5 vs. 39.4 +/- 4.4 micrograms/L; P < 0.001). Before puberty, there was no sex-dependent difference in the GH response to HEX. It increased during puberty (P < 0.05 and P < 0.002 for boys and girls, respectively), when it was higher (P < 0.05) in girls than in boys. In contrast, GH responses to GHRH were not related to sex differences and/or puberty. In conclusion, HEX is a potent and reproducible stimulus of GH secretion in children. The effect of HEX increases in puberty, with girls showing a more marked GH response.

Adolescent↗

PubMed1995

The effect of hexarelin on growth hormone (GH) secretion in patients with GH deficiency.

Hexarelin (Hex) is a new synthetic hexapeptide with potent GH-releasing activity in both animals and men. We evaluated the GH response to maximal doses of Hex (2 micrograms/kg, iv) and GHRH-(1-29) (1 microgram/kg, iv) in 15 children (11 boys and 4 girls, aged 6.0-17.3 yr) and 4 adults (3 men and 1 woman, aged 20.2-30 yr) with GH deficiency (GHD). GHD was idiopathic in 8 patients and associated with pituitary stalk interruption syndrome in 8, with a pituitary cyst in 2, and with empty sella syndrome in 1. In 11 patients, GHD was isolated, whereas in 8, it was associated with other pituitary hormone deficiencies. Forty-five short normal children (24 boys and 21 girls, aged 5.9-14 yr) served as controls. In patients with idiopathic GHD, the GH response to Hex was similar to that observed in short normal children, and it was significantly higher than the response to GHRH. In the patients with GHD associated with anatomical abnormalities, the GH responses to GHRH varied from normal to absent. Among these subjects, only 1 patient with a pituitary cyst had a sizable GH response to Hex, whereas in all others, the GH response to Hex was absent or blunted compared with those in the short normal children and the patients with idiopathic GHD. In all patients except those with associated ACTH deficiency, Hex administration caused a slight, but significant, increase in cortisol concentrations. This study shows that Hex stimulates GH secretion in patients with idiopathic GHD. The inability of Hex to stimulate GH secretion in patients with hypothalamic-pituitary disconnection strongly supports the concept that in humans, the GH-releasing effect of GH-releasing peptides is mediated by the hypothalamus.

Adolescent↗

PubMed1995

Comparison of the effects of growth hormone-releasing hormone and hexarelin, a novel growth hormone-releasing peptide-6 analog, on growth hormone secretion in humans with or without glucocorticoid excess.

The aim of our study was to investigate the effect of hexarelin, a novel GH-releasing peptide-6 analog, and GH-releasing hormone (GHRH) (alone or in combination) on GH secretion in adult patients with increased somatostatin tone due to chronic glucocorticoid excess. We studied seven adult patients undergoing long-term (no less than 6 months) immunosuppressive glucocorticoid treatment for non-endocrine diseases (six females and one male, age range 42-68 years) and one subject (female, age 31 years) with endogenous hypercortisolism due to adrenal adenoma. Six normal subjects (four females and two males) matched for sex and age with the patients and not undergoing any therapy served as controls. All the subjects underwent the following three tests in random order: (1) human GHRH (1-29)NH2 (100 micrograms in 1 ml saline) injected as an i.v. bolus at 0 min, (2) hexarelin (100 micrograms in 1 ml saline) injected as an i.v. bolus at 0 min and (3) hexarelin (100 micrograms in 1 ml of saline) plus GHRH (100 micrograms in 1 ml saline) injected as an i.v. bolus at 0 min. After GHRH alone the patients with glucocorticoid excess showed a blunted GH response as compared with normal subjects (median delta GH: 0.9, range 0-5.6 micrograms/l vs 7:1, range 0.3-14.9 micrograms/l). No significant differences were observed in the steroid-treated group with respect to normal subjects after hexarelin alone (median delta GH: 15.5, range 1.9-45.2 micrograms/l vs 17.9, range 5.5-53.9 micrograms/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Growth hormone-releasing activity of hexarelin in humans. A dose-response study.

Hexarelin is a new hexapeptide (His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2) that stimulates the release of growth hormone both in vitro and in vivo. In this double-blind, placebo-controlled, rising-dose study we evaluated the growth hormone releasing activity of hexarelin in healthy human subjects. Twelve adult male volunteers received single intravenous boluses of 0.5, 1 and 2.micrograms.kg-1 hexarelin as well as placebo. For safety, drug doses were given in a rising-dose fashion with placebo randomly inserted into the sequence. Plasma growth hormone concentrations increased dose-dependently after the injection of the peptide, peaking at about 30 min and then decreasing to baseline values within 240 min with a half-life of about 55 min. The mean peak plasma growth hormone concentrations (Cmax) were 3.9, 26.9, 52.3, 55.0 ng.ml-1 after 0, 0.5, 1 and 2 micrograms.kg-1, respectively. The corresponding areas under the curve of growth hormone plasma levels from drug injection to 180 min (AUC0-180) were 0.135, 1.412, 2.918 and 3.695 micrograms.min.ml-1. The theoretical maximum response (Emax) and the dose that produces half of the maximum response (ED50) were estimated using logistic regression. The calculated ED50 values were 0.50 and 0.64 microgram.kg-1 for Cmax and AUC0-180, respectively. The corresponding Emaxs were 55.1 ng.ml-1 and 3936 ng.min.ml-1, thus indicating that the effect after the 2 micrograms.kg-1 dose is very close to the maximal response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

GH-releasing activity of Hexarelin, a new growth hormone releasing peptide, in infant and adult rats.

In recent years several synthetic peptides have been shown to be active in inducing GH secretion in different mammalian species. Among them GHRP-6, GHRP-1 and GHRP-2 have demonstrated high effectiveness and high selectivity in stimulating GH release. In the present paper we report studies on the GH-secreting properties of a GHRP analog in which Trp was substituted with the chemically more stable 2-Methyl-Trp. In studies performed in conscious 10-day old rats, the hexapeptide Hexarelin (His-D-2Me-Trp-Ala-Trp-D-Phe-Lys-NH2) resulted very active in stimulating GH secretion. In anesthetized adult male rats, i.v. administration of GHRP-6 or Hexarelin elicited prompt GH release with peak GH levels occurring within 10 min At all the doses tested, the 2 peptides possessed similar effectiveness in stimulating GH release. Hexarelin given s.c. elicited a long-lasting GH release and was slightly more effective than GHRP-6. In conclusion, these findings indicate that Hexarelin is a highly effective GH releaser and might represent a valuable diagnostic and/or therapeutic tool in clinical practice.

Aging↗

PubMed1994

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

OBJECTIVE: Hexarelin is a new synthetic growth hormone releasing peptide. We have tested the efficacy of intranasal (i.n.) administration of hexarelin to stimulate plasma GH and have compared this to the intravenous (i.v.) administration of the peptide. PATIENTS: Ten children with familial short stature (FSS) aged 5.5-15.5 years and two known GH deficient patients aged 24 and 28 years without GH treatment. METHODS: All 12 subjects were submitted to i.v. (1 microgram/kg) and i.n. (20 micrograms/kg) hexarelin tests with a one-week interval between tests. Blood samples for GH, TSH, fT4 and T3 were obtained at 0, 15, 30, 60, 90 and 120 minutes. The hormone determinations were made by standard radio-immunoassays (RIA). RESULTS: Both the i.n. and i.v. administration of hexarelin induced a large GH response, the mean (+/- SD) being 72.2 +/- 35.5 mU/l for the i.n. test and 79.6 +/- 53.0 mU/l for the i.v. test. The peak GH in the i.v. test occurred at 15-30 minutes and in the i.n. test between 30 and 60 minutes. The GH deficient patients showed no GH response in either test. Plasma TSH decreased in the FSS children from a mean (+/- SD) of 1.0 +/- 0.26 to 0.64 +/- 0.2 mU/l (P < 0.005) during the i.n. test and from 1.0 +/- 0.3 to 0.7 +/- 0.3 mU/l (P < 0.05) during the i.v. test. In the isolated GH deficient patient, plasma TSH decreased from 1.06 +/- 0.38 mU/l to 0.86 +/- 0.17 during the i.v. test and from 1.60 +/- 0.01 to 1.11 +/- 0.06 mU/l during the i.n. test. There were no significant changes in plasma fT4 or T3 in any of the tests. CONCLUSIONS: The synthetic hexapeptide hexarelin is a potent pituitary GH stimulator when administered intranasally. The GH response was similar to that observed after intravenous hexarelin. Simultaneously, there was a significant decrease in plasma TSH but the concentrations remained in the normal range. These findings appear to be of theoretical and practical relevance to the investigation and management of short children.

Administration, Intranasal↗

PubMed1994

Growth hormone (GH)-releasing hormone secretion is stimulated by a new GH-releasing hexapeptide in sheep.

The acute effect of a new GH-releasing peptide, hexarelin (1 mg, iv), on GH secretion and the mechanisms involved in its changes were investigated in conscious sheep. Peripheral GH levels and GH-releasing hormone (GHRH) and somatostatin concentrations in hypophysial portal blood were measured in six rams. An increase in jugular GH levels was observed 15 min after hexarelin injection (9.1 +/- 1.8 vs. 3.9 +/- 0.8 ng/ml; P < 0.05). This was associated with a stimulation of GHRH release into hypophysial portal blood (145.4 +/- 19.9 vs. 59.2 +/- 10.8 pg/ml; P < 0.01) without a change in somatostatin secretion. Our data indicate that GH-releasing peptide-induced GH stimulation in the sheep involves an activation of GHRH neurons in addition to the previously demonstrated direct effect on the pituitary cells.

Animals↗

PubMed1994

Growth hormone-releasing activity of hexarelin, a new synthetic hexapeptide, after intravenous, subcutaneous, intranasal, and oral administration in man.

We evaluated the GH-releasing activity of hexarelin, a new synthetic hexapeptide, after i.v. (1 and 2 micrograms/kg), sc (1.5 and 3 micrograms/kg), intranasal (20 micrograms/kg), and oral (po; 20 and 40 mg) administration to 12 healthy young volunteers. Reference treatments were i.v. saline and GH-releasing hormone (GHRH; 1 microgram/kg). GH release (mean +/- SEM) after the i.v. dose of 1 microgram/kg hexarelin [area under the curve (AUC), 3175 +/- 506 micrograms/min.L] was about 2 times higher than that induced by 1 microgram/kg GHRH (AUC, 1544 +/- 161 micrograms/min.L; P < 0.001). Hexarelin (2 micrograms/kg, i.v.) elicited a further increase in GH levels (AUC, 4422 +/- 626 micrograms/min.L) compared to the 1 microgram/kg dose. The GH response to 2 micrograms/kg hexarelin, i.v., was very reproducible (AUC, 4016 +/- 563 vs. 3959 +/- 803 micrograms/min.L). The sc administration of hexarelin produced a dose-dependent GH response (AUC, 3180 +/- 392 and 4459 +/- 566 micrograms.min.L with 1.5 and 3 micrograms/kg, respectively). Intranasal administration of 20 micrograms/kg hexarelin induced GH release (AUC, 2642 +/- 452 micrograms/min.L) similar to that caused by 1 microgram/kg, i.v. Twenty and 40 mg hexarelin, po, produced a dose-related increase in GH levels (AUC, 2278 +/- 442 and 4079 +/- 514 micrograms/min.L). Biological bioavailabilities were 77.0 +/- 10.5%, 4.8 +/- 0.9%, and 0.3 +/- 0.1% for the sc, intranasal, and po routes, respectively. This study shows that the GH response to hexarelin administered by the i.v. route has a limited variability and is superior to the response to GHRH. The GH-releasing activity appeared to be dose dependent. Thus, hexarelin could be clinically useful to stimulate GH secretion in humans.

Administration, Intranasal↗