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Biomedical subjects

F Camanni

Publications and source records attributed to F Camanni.

At least 109 records · Page 6Linked to original sources
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

Effect of 15-day treatment with growth-hormone-releasing hormone alone or combined with different doses of arginine on the reduced somatotrope responsiveness to the neurohormone in normal aging.

It is well known that both spontaneous and growth hormone-releasing hormone (GHRH)-stimulated GH secretion undergo an age-related decrease; in addition, there is supportive evidence that the GH hyposecretory state of aging is of hypothalamic origin. The aims of the study in 35 normal elderly subjects (20 males and 15 females aged 65-89 years) were to verify whether the low somatotrope responsiveness to GHRH (1 microgram/kg) can be primed by a daily GHRH treatment and whether the potentiating effect of both high intravenous (0.5 g/kg) and low oral (8 g) doses of arginine (ARG) on GH response to GHRH is maintained with time. In group A (N = 14) the GH response to GHRH on day 1 (AUC: 373.5 +/- 78.5 micrograms.l-1.h-1) was unchanged after 7 (3720 +/- 38 micrograms.l-1.h-1) and 15 days (377.9 +/- 63.8 micrograms.l-1.h-1) of daily GHRH administration. In group B (N = 6) the GH response to GHRH co-administered with iv ARG on day 1 (1614.2 +/- 146.2 micrograms.l-1.h-1) was higher (p < 0.05) than that of GHRH alone (group A) and persisted unchanged after 7 (1514.7 +/- 366.5 micrograms.l-1.h-1) and 15 days (1631.7 +/- 379.1 micrograms.l-1.h-1) of treatment. In group C (N = 15) the GH response to GHRH co-administered with oral ARG on day 1 (950.6 +/- 219.4 micrograms.l-1.h-1) was higher (p < 0.03) than that of GHRH alone (group A) but lower (p < 0.05) than that to GHRH plus iv ARG (group B).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

Effect of galanin on basal and stimulated secretion of prolactin, gonadotropins, thyrotropin, adrenocorticotropin and cortisol in humans.

Galanin enhances both baseline and growth hormone-releasing hormone (GHRH)-induced GH secretion both in animals and in man. Although galanin has a clear influence on the secretion of other anterior pituitary hormones in animals, in man it increases prolactin (PRL) slightly but does not affect spontaneous thyrotropin (TSH), luteinizing hormone (LH), follicle-stimulating hormone (FSH) or adrenocorticotropin (ACTH) secretion. The aim of our study was to verify the effect of galanin on basal and releasing hormone-stimulated release of gonadotropins, PRL, TSH, ACTH and cortisol secretion. As GH release has been shown to be inhibited by corticotropin-releasing hormone (CRH), we also studied the effect of CRH on galanin-stimulated GH increase. The effect of porcine galanin (15 micrograms/kg iv infused in 60 min) alone and in combination with thyrotropin-releasing hormone (TRH, 200 micrograms iv bolus), CRH (100 micrograms iv bolus) and gonadotropin-releasing hormone (GnRH, 100 micrograms iv bolus) on GH, PRL, TSH, ACTH, cortisol, FSH and LH secretion in seven normal young women (aged 25-30 years) was studied. Galanin infusion caused an increase in serum GH levels (p < 0.02) but failed to modify significantly the spontaneous PRL, LH, FSH, TSH, ACTH and cortisol secretion. The combined administration of TRH, GnRH and CRH caused a significant increase in PRL (p < 0.02), LH (p < 0.02), FSH (p < 0.02), TSH (p < 0.02), ACTH (p < 0.02) and cortisol (p < 0.05), but not in GH levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1995

Involvement of brain catecholamines and acetylcholine in growth hormone hypersecretory states. Pathophysiological, diagnostic and therapeutic implications.

Secretion of growth hormone (GH) is excessive in acromegaly, but also in a number of other pathological states such as anorexia nervosa, insulin-dependent diabetes mellitus (IDDM), liver cirrhosis, depression, renal failure and GH-insensitivity syndrome. Abnormalities in the neuroendocrine control of GH secretion and/or a state of insensitivity to GH contribute to hypersecretion of GH in these states, with the possible exception of acromegaly, which appears to be a primary pituitary disease. GH hypersecretion may also occur in neonates or adolescents with tall stature, thus reflecting particular physiological or paraphysiological conditions. In the cohort of brain neurotransmitters, catecholamines and acetylcholine reportedly play a major role in the control of neurosecretory GH-releasing hormone (GHRH) and somatostatin (SS)-producing neurons, and hence GH secretion. Activation of alpha 2-adrenoceptors or of muscarinic cholinergic receptors in the hypothalamus stimulates GH release, probably through stimulation of GHRH and inhibition of SS release, respectively. Activation of dopamine receptors likewise stimulates GH release, while activation of beta-receptors inhibits GH release through stimulation of hypothalamic SS function. This review discusses the involvement of brain catecholamines and acetylcholine in GH hypersecretory states, including anorexia nervosa, acromegaly, IDDM, liver cirrhosis, depression, renal failure and GH insensitivity syndrome, with a view to providing a fuller understanding of their pathophysiology and, whenever possible, diagnostic and therapeutic implications.

Acetylcholine↗
PubMed1995

Effect of arginine and pyridostigmine on the GHRH-induced GH rise in obesity and Cushing's syndrome.

OBJECTIVES: The aim of this work was to clarify the mechanisms underlying growth hormone (GH) hyposecretion in Cushing's syndrome (CS) and in obesity. We studied the GH response to GH-releasing hormone (GHRH) alone and combined with arginine or pyridostigmine, two substances likely to inhibit hypothalamic somatostatin release. DESIGN: Three tests with GHRH alone (1 microgram/kg i.v. at 0 min) and combined with arginine (ARG, 0.5 g/kg infused over 30 min) or pyridostigmine (PD, 120 mg orally at -60 min) were performed 3 days apart and in random order in eight women with CS (five with ACTH-dependent and three with ACTH-independent hypercortisolism, age 18-56, BMI 26.1 +/- 1.5 Kg/m2) and 11 with OB (age 17-54, BMI 42.9 +/- 2.2 Kg/m2). Eleven normal women (age 23-50, BMI 21.9 +/- 0.3 Kg/m2) were studied as controls (C). MEASUREMENTS: Serum GH and IGF-I levels were measured by radioimmunoassay. The GH secretory responses were expressed either as absolute values (micrograms/L) or as areas under the curve (AUC, micrograms/L/h) calculated by trapezoidal integration. IGF-I concentrations were expressed as absolute values (micrograms/L) with reference to a pure recombinant IGF-I preparation. RESULTS: Basal GH levels in CS were similar to those registered in OB (mean +/- s.e.m. 0.7 +/- 0.1 vs 0.9 +/- 0.2 microgram/L) and lower than in C (3.4 +/- 0.5 microgram/L, P < 0.00001). On the other hand, IGF-I levels were similar in all groups. The GHRH-induced GH rise in CS was lower, though not significantly, to that observed in OB (AUC: 65.6 +/- 13.2 vs 192.5 +/- 61.7 microgram/L/h) and both GH responses were significantly lower than that of C (1029.9 +/- 98.0 micrograms/L/h, P < 0.00001). ARG enhanced the GHRH-induced GH release in CS (331.9 +/- 51.9 micrograms/L/h vs GHRH alone, P < 0.0001), OB (852.4 +/- 162.1 micrograms/L/h, P < 0.0001) and C (3362.6 +/- 386.0 micrograms/L/h, P < 0.0002). However, the GH response to GHRH plus ARG in CS was lower (P < 0.002) than that in OB which, in turn, was lower than that in C (P < 0.00001). Pyridostigmine significantly enhanced the GHRH-induced GH rise in C (2808.5 +/- 221.2 micrograms/L/h, P < 0.00001) and, to a lesser extent, in OB (627.3 +/- 84.7 micrograms/L/h, P < 0.0002) but not in CS (102.9 +/- 25.0 micrograms/L/h). CONCLUSIONS: Our results indicate that the GH releasable pool is reduced in obesity and, to an even greater extent, in Cushing's syndrome. The inability of pyridostigmine and arginine to restore a normal GH response to GHRH in these conditions makes the existence of a hypothalamic somatostatinergic hyperactivity unlikely.

Adolescent↗
PubMed1995

A new approach in the evaluation of gonadotropins for the diagnosis of polycystic ovary syndrome.

The new immunometric methods using monoclonal antibodies to detect gonadotropins revealed a reduction in the absolute values of these hormones, especially LH, due to a decrease in cross-reaction between gonadotropin subunits. Therefore, reference values of the LH/FSH ratio and their diagnostic significance in the polycystic ovary syndrome (PCOS) need to be defined again. We evaluated the LH/-FSH ratio in basal conditions and after administration of GnRH (100 micrograms as i.v. bolus) in seventy patients with PCOS employing an immunoenzymatic method. In PCOS patients the LH/FSH ratio was greater than 1 in 70% when evaluated on a single sample and in 88% when evaluated on a pooled serum from four samples every 30 minutes; in the control group the ratio was always lower than 1. The LH/-FSH ratio evaluated on the peak values in response to GnRH was greater than 2 in all patients and lower than 2 in the control group. Our results indicate that the LH/FSH ratio is still an important diagnostic tool in PCOS, especially when evaluated on the peak values in response to GnRH, even if its reference values are lower using these new monoclonal methods.

Adolescent↗
PubMed1994

Arginine but not pyridostigmine, a cholinesterase inhibitor, enhances the GHRH-induced GH rise in patients with anorexia nervosa.

Pirenzepine, a muscarinic antagonist probably acting via stimulation of hypothalamic somatostatin release, abolishes the growth hormone releasing hormone (GHRH)-stimulated growth hormone (GH) rise in normal subjects but only blunts it in patients with anorexia nervosa (AN). This finding suggested the existence in AN of an alteration of cholinergic system and/or somatostatinergic tone. To further investigate these mechanisms, in 11 AN women patients (age 18.8 +/- 0.9 years; BMI 13.4 +/- 0.4) we studied the GH response alone (1 microgram/Kg IV as a bolus at 0 min) and combined with pyridostigmine (PD, 120 mg orally, 60 min before GHRH administration), a cholinesterase inhibitor, or arginine (ARG 30 g infused over 30 min starting at 0 min), two compounds probably acting via inhibition of hypothalamic somatostatin (SS) release. The GH response to GHRH preceded by a previous (120 min before) neurohormone administration also was studied. All these tests also were performed in 20 normal age-matched women (age 22.0 +/- 1.8 yrs; BMI20.1 +/- 2.4). Basal serum GH levels were higher in AN patients than in normal volunteers (NV) (10.3 +/- 3.4 versus 2.8 +/- 0.3 microgram/L; p < 0.001), whereas plasma IGF-I levels were lower in AN patients than in NV (43.3 +/- 10.6 versus 172.4 +/- 13.9 micrograms/L; p < 0.00001). In AN patients, GHRH administration induced a GH rise higher, though not significantly, than that in NV [delta area under the curve (AUC) 1173.6 +/- 167.6 versus 834.6 +/- 188.1 micrograms/L/h]. The GH response to the second of two consecutive GHRH boluses was lower (p < 0.01) than that of the first one either in AN patients or in NV (67.6 +/- 27.4 and 53.1 +/- 25.7 micrograms/L/h, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Effects of direct and indirect acetylcholine receptor agonists on growth hormone secretion in humans.

Cholinergic pathways in the central nervous system positively influence growth hormone (GH) secretion. In fact pyridostigmine, a cholinesterase inhibitor, enhances both basal and GH-releasing hormone (GHRH)-induced GH secretion while, conversely, pirenzepine, an antagonist of muscarinic M1 receptors, inhibits the GH response to GHRH and to other physiological and pharmacological stimuli. The effect of the cholinergic system on GH secretion probably takes place via inhibition of the release of endogenous somatostatin. In this study in 36 normal adults (26 males and 10 females, age 22-35 years) we compared the effects of three cholinesterase inhibitors (pyridostigmine, 120 mg p.o., n = 19; neostigmine, 10 micrograms/kg i.v., n = 6; physostigmine, 12.5 micrograms/kg i.v., n = 6) and bethanechol, a direct muscarinic receptor agonist that is mainly active on muscarinic M3 receptors (25 micrograms/kg i.v., n = 5), on both basal and GHRH (1 microgram/kg i.v.)-stimulated GH secretion. Pyridostigmine, neostigmine and physostigmine induced a significant GH increase (peak vs. basal levels, mean +/- S.E.: 10.4 +/- 1.6 vs. 0.6 +/- 0.2 micrograms/l, P = 0.0001; 13.3 +/- 1.2 vs. 0.5 +/- 1.1 micrograms/l, P = 0.004; and 14.9 +/- 3.1 vs. 2.7 +/- 1.1 micrograms/l, P = 0.025;, respectively). These drugs also induced a similar potentiation of the GH response to GHRH (peak: 48.3 +/- 5.6 vs. 16.2 +/- 2.2 micrograms/l, P = 0.0001; 49.2 +/- 2.2 vs. 19.9 +/- 5.1 micrograms/l, P = 0.006; and 76.9 +/- 12.4 vs. 18.1 +/- 5.3 micrograms/l, P = 0.001, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Low doses of either intravenously or orally administered arginine are able to enhance growth hormone response to growth hormone releasing hormone in elderly subjects.

Reportedly, the responsiveness of somatotrope cells to GHRH is reduced in elderly humans but it is totally restored by arginine (ARG) which likely acts by inhibiting hypothalamic release of somatostatin. As this effect was observed after infusion of high doses of the amino acid, in this study, we compared the effect of iv administration of 30, 10 and 5 g ARG(group A, B and C, respectively) as well as oral administration of 8 g ARG(group D) on the GH response to 1 microgram/kg i.v.GHRH in 27 healthy elderly subjects (11 M and 16 F, age 70-86 yr, BMI 21-25 kg/m2). In group A (n = 7) 30 g i.v. ARG strikingly enhanced the GHRH-induced GH rise (peak, mean +/- SE: 41.5 +/- 4.4 vs 11.7 +/- 5.3 micrograms/L, p < 0.05). Similarly, in group B (n = 6) and D (n = 7) 10 g i.v. and 8 g oral ARG enhanced the GH response to GHRH (20.9 +/- 4.7 vs 8.3 +/- 2.8 micrograms/L, p < 0.03 and 31.0 +/- 5.3 vs 11.4 +/- 3.4 micrograms/L, p < 0.03, respectively). In contrast, in group C (n = 7) 5 g i.v. ARG failed to modify the GHRH-induced GH rise (6.0 +/- 1.6 vs 3.5 +/- 0.9 micrograms/L). The GH responses to GHRH alone did not significantly differ amongst groups; the GH responses to GHRH and ARG were not significantly different among groups A, B and D and were greater than the GH response in group C. These results show that the GH response to GHRH in elderly subjects is enhanced even by low iv doses of arginine and by the orally administered amino acid, the lowest effective dose being 8 g. Moreover, they imply that the combined administration of GHRH and arginine may be a useful approach to restore the impaired function of the GH-IGF axis in aging.

Administration, Oral↗
PubMed1994

Arginine enhances the growth hormone-releasing activity of a synthetic hexapeptide (GHRP-6) in elderly but not in young subjects after oral administration.

In man the GH-releasing hexapeptide His-DTrp-Ala-Trp-DPhe-Lys-NH2 (GHRP-6) has been shown to be active even after oral administration. On the other hand, it has been shown that arginine (ARG) totally restores the reduced somatotropic responsiveness to GHRH observed in aging. Based on the foregoing, in this study we verified the GH-releasing activity of oral GHRP-6 (300 micrograms/kg) in normal aging and the possible enhancing effect of 8 g oral ARG on the GH-releasing effect of GHRP-6. Eight young (age 24-32 yr) and 8 elderly (age 66-85 yr) subjects were studied. In all the GH response to GHRH (1 microgram/kg iv) was also studied. Both IGF-I levels and the GH response to iv GHRH were lower in elderly than in young subjects (mean +/- SE, IGF-I: 65.1 +/- 9.1 vs 142.9 +/- 9.4 micrograms/L, p < 0.0001; GH peak: 5.4 +/- 1.0 vs 13.6 +/- 0.8 micrograms/L, p < 0.0001). Oral GHRP-6 administration induced a GH rise in elderly which was lower, though not significantly, than that in young subjects (GH peak: 9.9 +/- 2.0 vs 16.2 +/- 5.4 micrograms/L). Oral ARG administration enhanced the GHRP-6-induced GH rise in elderly (GH peak: 22.1 +/- 3.3 micrograms/L, p < 0.01 vs GHRP-6 alone) while failed to modify it in young subjects (GH peak: 13.5 +/- 3.4 micrograms/L). The GH response to oral ARG+GHRP-6 in elderly was higher than that to all stimuli in young adults (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1994

Interaction of free fatty acids and arginine on growth hormone secretion in man.

We studied the interaction between free fatty acids (FFAs) and arginine (ARG) on basal and growth hormone (GH)-releasing hormone (GHRH)-stimulated GH secretion in 14 normal subjects. Compared with placebo, ARG induced a significant increase of GH secretion (334.0 +/- 157.5 v 36.9 +/- 27.6 micrograms/L/h, P < .05). The increased levels of FFAs (1.9 +/- 0.4 mEq/L), obtained by the infusion of a lipid-heparin emulsion, abolished the effect of ARG (55.8 +/- 45.6 v 334.0 +/- 157.5 micrograms/L/h, P < .05). GHRH-induced GH secretion was potentiated by ARG (2,009.9 +/- 463.2 v 922.0 +/- 244.4 micrograms/L/h, P < .05) and suppressed by lipid-heparin infusion (106.2 +/- 28.3 v 922.0 +/- 244.4 micrograms/L/h, P < .01). Moreover, the lipid-heparin infusion inhibited the potentiating effect of ARG on the GHRH-induced GH increase (527.9 +/- 113.6 v 2,009.9 +/- 463.2 micrograms/L/h, P < .01). These results confirm the strong inhibitory effect of FFAs on GH secretion, showing that they are even able to inhibit the potentiating effect of ARG on the GH response to GHRH. Since ARG likely acts via inhibition of hypothalamic somatostatin release, the inhibitory effect of FFAs on GH secretion could take place directly at the pituitary level and/or at the hypothalamic level, counteracting the effect of ARG.

Adult↗
PubMed1994

Pirenzepine decreases basal and stimulated GH secretion in patients with type 2 (non-insulin-dependent) diabetes mellitus.

Growth hormone (GH) hypersecretion has been described in diabetes mellitus and seems to be involved in the pathogenesis of diabetes complications. As pirenzepine (PZ), a cholinergic muscarinic antagonist, is able to inhibit GH hypersecretion in insulin-dependent diabetes mellitus (IDDM), we investigated whether PZ is also able to inhibit spontaneous and stimulated GH-release in non-insulin-dependent diabetes mellitus (NIDDM). Ten non-obese well-controlled patients with NIDDM underwent in random order the following three double-blind one week treatments: placebo (PL), PZ at low dose (PL in the morning plus PZ 50 mg at 22 h) or high dose (PZ 50 mg at 8 h plus 100 mg at 22 h). Pirenzepine administration significantly (p < 0.05) decreased nocturnal GH release after both low and high dose (AUC, PL vs PZ: 107.3 +/- 26.5 vs 48.3 +/- 10.5 and 57.6 +/- 9.6 micrograms/L/h, respectively). The GH response to arginine infusion was significantly inhibited by PZ at high dose (AUC, 147.1 +/- 48.8 vs 444.7 +/- 194.3 micrograms/L/h, p < 0.01), but not at low dose. Glucose, insulin, glucagon and somatostatin responses to arginine infusion were not changed by pirenzepine treatment. In conclusion, the muscarinic blockade by PZ is able to inhibit the spontaneous and stimulated GH secretion also in NIDDM without affecting insulin secretion.

Adult↗
PubMed1994

Double blind randomized study using oral or injectable bromocriptine in patients with hyperprolactinaemia.

OBJECTIVE: A new long-acting injectable form of bromocriptine has become available for long-term treatment of hyperprolactinaemic patients. The objective of this study was to compare efficacy and tolerability of injectable and oral forms of bromocriptine. DESIGN: A double-blind randomized study. All patients received either one injection of bromocriptine 50 mg intramuscularly and placebo tablets for 28 days (Group A) or one placebo injection and oral bromocriptine 7.5 mg daily for 28 days (Group B). PATIENTS: Twenty-three (12 patients for Group A and 11 patients for Group B) hyperprolactinaemia patients with (19 patients) or without (4 patients) CT/MRI evidence of tumour were studied. MEASUREMENTS: Plasma PRL levels and serum bromocriptine levels were assessed during a follow-up of 42 days. MRI and/or CT were evaluated before and 28 days after the beginning of the study. RESULTS: All patients had significant reductions of PRL levels from 1000 h and 1100 h of day 1 to 2000 h of day 35. Normoprolactinaemia was shown in eight patients of Group A and six of Group B on days 1-28. Normal PRL levels were still present in five patients of Group A and in one patient of Group B on day 35; only three patients of Group A had normoprolactinaemia on day 42. A significantly greater decrease in Group A in comparison with Group B was shown at 1200 h on day 1 and at all times as a percentage decrease from basal levels. Significantly higher levels of bromocriptine were shown in Group A at all timepoints studied. No difference was shown in tolerability and incidence of side-effects. CONCLUSION: Our data show that injectable bromocriptine more frequently induced a prolonged normoprolactinaemia than did the oral drug. Moreover, bromocriptine levels released during injectable bromocriptine were significantly higher than during oral bromocriptine. On the other hand no difference was shown in the tolerability of bromocriptine according to the route of administration.

Administration, Oral↗
PubMed1994

Interaction of salbutamol with pyridostigmine and arginine on both basal and GHRH-stimulated GH secretion in humans.

OBJECTIVE: It is well known that acetylcholine and arginine stimulate GH secretion while activation of beta-adrenergic receptors inhibits GH secretion in man. We aimed therefore to ascertain whether or not the inhibitory influence of beta-adrenergic receptors on GH secretion would over-ride the stimulatory one of acetylcholine and arginine. DESIGN: We studied the interaction of salbutamol, a beta 2-adrenergic agonist (SAL, 0.08 mg/kg orally) with pyridostigmine, a cholinesterase inhibitor (PD, 120 mg orally), or arginine (0.5 g/kg i.v.) on both basal and GHRH (1 microgram/kg i.v.)-stimulated GH secretion. SUBJECTS: Fourteen healthy male volunteers, aged 20-35 years, were studied. MEASUREMENTS: Serum GH was measured in duplicate by immunoradiometric assay. RESULTS: In study A, SAL inhibited the GH response both to GHRH (P < 0.01) and ARG (P < 0.002). ARG enhanced the GHRH-induced GH rise (P < 0.01) but its effect was abolished (P < 0.02) by SAL pretreatment. In study B, SAL inhibited the GH response both to GHRH (P < 0.01) and PD (P < 0.02). PD enhanced the GH response to GHRH (P < 0.001) but its effect was abolished (P < 0.05) by SAL pretreatment. In both studies, the GH response to GHRH alone was similar to that to the neurohormone when combined with ARG + SAL or PD + SAL. CONCLUSION: Our results show that beta 2-adrenergic activation by salbutamol is able to inhibit not only the GH rise induced by GHRH, arginine and pyridostigmine, but even the potentiating effect of both arginine and pyridostigmine on the GH response to GHRH. They indicate that catecholamines, acetylcholine and arginine play a major role in GH secretion having opposite influences aimed to balance the function of the hypothalamus-GH-IGF-I axis in man.

Adult↗
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↗
PubMed1994

Arginine and growth hormone-releasing hormone restore the blunted growth hormone-releasing activity of hexarelin in elderly subjects.

Although both spontaneous and stimulated GH secretion undergo an age-related decline, the secretory capacity of somatotrope cells is preserved in human aging. In the present study we compared the GH responses to hexarelin, GHRH, and the combined administration of hexarelin and GHRH or arginine in young and elderly subjects. Thirteen young (24- to 30-yr-old) and 16 elderly (65- to 84-yr-old) normal males were divided into 2 groups. The first group (7 young and 8 elderly subjects) received the following as single iv injections during 3 different treatment sessions: hexarelin (2 micrograms/kg), GHRH (2 micrograms/kg), or hexarelin (2 micrograms/kg) plus GHRH (2 micrograms/kg). The second group (6 young and 8 elderly subjects) was administered single iv injections of hexarelin (2 micrograms/kg) or hexarelin (2 micrograms/kg) plus arginine (0.5 g/kg) during 2 different treatment sessions. In both groups basal IGF-I levels in the elderly were lower than those in young subjects (114.5 +/- 18.7 vs. 211.5 +/- 19.1 micrograms/L; P < 0.001). In the first group the GH response to hexarelin was greater in young compared to elderly subjects (area under the curve from 0-120 = 4849 +/- 601 vs. 2112 +/- 683 micrograms.min/L; P < 0.001). GHRH elicited a lower GH response than that induced by hexarelin in both young (1455 +/- 102 micrograms/h.L; P < 0.02) and elderly subjects (563 +/- 87 micrograms/min.L; P < 0.02). GHRH potentiated the somatotrope response to hexarelin in both young (7725 +/- 503 micrograms/min.L; P < 0.02) and elderly subjects (3895 +/- 612 micrograms/min.L; P < 0.02), but to a lesser extent in the latter (P < 0.001). In the second group, the GH response induced by hexarelin was also higher in young subjects than in elderly subjects (4819 +/- 668 vs. 1649 +/- 459 micrograms/min.L; P < 0.001). The GH response to hexarelin was potentiated by arginine in elderly (4139 +/- 1057 micrograms/min. L; P < 0.001), but not in young subjects (4743 +/- 774 micrograms/min.L). This study shows that the maximal effective dose of hexarelin releases more GH than the maximal effective dose of GHRH in both normal young and elderly subjects. The effect of hexarelin on GH secretion is age dependent, and the GH response to the combined administration of hexarelin and GHRH was significantly higher in young subjects compared to elderly subjects. Arginine does not potentiate the GH response to hexarelin in young subjects, whereas it significantly enhances it in elderly subjects.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

Enhanced adrenocorticotrophic hormone and cortisol responses to corticotrophin-releasing hormone in central idiopathic diabetes insipidus.

It is well known that arginine vasopressin (AVP) exerts a stimulatory effect on adrenocorticotrophic hormone (ACTH) secretion. Moreover, there is consistent evidence that the hypothalamic AVP-secreting neurons are involved in the neuroregulation of ACTH secretion. With the aim to throw further light on the interaction between AVP and corticotrophin-releasing hormone (CRH) in the neuroregulation of ACTH secretion, in this study we compared the ACTH and cortisol responses to human CRH (100 micrograms iv as a bolus) in 18 normal subjects (15 females and three males, age 22-35 years) and seven patients with central isolated diabetes insipidus (six females and one male, age 16-40 years). Two patients were newly diagnosed and five had discontinued substitution therapy with desamino-D-AVP 24 h before testing. All had free access to water before and during the test period. The ACTH and cortisol responses to CRH were higher in subjects with diabetes insipidus than in controls, either when evaluated as peak values (ACTH, mean +/- SEM: 17.0 +/- 1.2 vs 7.7 +/- 0.7 pmol/l, p = 0.0003; cortisol: 611.3 +/- 59.4 vs 450.7 +/- 21.2 nmol/l, p = 0.01) or area under curve values (ACTH: 672.5 +/- 75.7 vs 364.0 +/- 33.6 pmol.l-1 x h-1, p = 0.002; cortisol: 29158.0 +/- 2937.0 vs 23236.7 +/- 1052.1 nmol.l-1 x h-1, p = 0.03). These results show that patients with diabetes insipidus have an exaggerated pituitary-adrenal response to CRH. This may be due to the fact that in diabetes insipidus AVP secretion from parvocellular neurons of the paraventricular nucleus in the hypophysial portal system is not impaired.(ABSTRACT TRUNCATED AT 250 WORDS)

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