Biomedical subjects

A Peñalva

Publications and source records attributed to A Peñalva.

At least 19 recordsLinked to original sources

PubMed2002

Presence of bovine leptin in edible commercial milk and infant formula.

Leptin is a hormone secreted by the adipocytes that contribute to the control of energy balance, and circulating leptin levels reflect the amount of adipose tissue in the body, helping to regulate food intake and energy expenditure. Since it has been shown that human milk contains immunoreactive leptin, which is identical to intact human leptin, we decided to investigate the possible presence of immunoreactive bovine leptin in different kinds of common commercial milk. To determine the presence or absence of immunoreactive leptin in bovine milk for human consumption, 81 samples (66 commercial pasteurized milk and 15 artificial formulae for new-born babies) of the most common Spanish commercial types of milk were studied. All samples were evaluated before and after centrifugation, and leptin levels were measured by RIA. Leptin was detected in all samples and RIA standard curves were not perturbed when centrifuged and non-centrifuged milk replaced the buffer. Mean values of leptin in full-cream, semi-skimmed and skimmed samples, were: 5.7+/-0.3 ng/ml, 4.1+/-0.1 ng/ml, 3.7+/-0.1 ng/ml (significantly different). Leptin values were reduced after centrifugation. A significant correlation was observed between leptin levels and lipid content (p<0.0005, r=0.67) while no correlation was observed with respect to carbohydrate and protein levels. Interestingly, some preparations of infant formulae present very high leptin values reaching up to 18.9 ng/ml. In conclusion, leptin is present in significant and variable concentrations in edible commercial bovine milk, with higher concentrations in infant formula.

Animals↗

PubMed2001

Effect of acute pharmacological modulation of plasma free fatty acids on GH secretion in acromegalic patients.

OBJECTIVES: In acromegaly GH secretion is markedly increased due in most cases to a GH secreting pituitary adenoma. GH secretion is modulated by variations in the levels of free fatty acids (FFA). Recent studies in different clinical situations, have shown that reduction in FFA with acipimox (A) modifies somatotroph cell responsiveness. The aim of the present study was to evaluate the effect of acute pharmacological reduction of plasma FFA on both basal GH levels and GHRH-mediated GH secretion in acromegalic patients. PATIENTS: Six acromegalic patients (four female, two male) aged 57 +/- 4 years., with active disease due to pituitary adenomas were studied. Four of the patients had been treated previously by surgery and/or radiotherapy. The diagnosis of active acromegaly was established by clinical assessment, increased serum IGF-I and impaired GH suppression after oral glucose. MEASUREMENTS: Four tests were performed: placebo, A (250 mg, orally, - 210 minutes and - 60 minutes), GHRH (100 microg, iv, 0 minutes) and GHRH plus A. The different tests on each subject were performed in random order one week apart, each subject served as their own control. Serum GH was measured by RIA at appropriate intervals. The area under the curve (AUC) was calculated by the trapezoidal METHOD: Statistical analysis was performed by Wilcoxon test. P < 0.05 was considered significant. RESULTS: The administration of A induced a FFA reduction during the entire test both when administered with placebo and with GHRH: AUC (mmol/l x 90 minutes): placebo plus placebo: 88.2 +/- 7.3. Placebo plus A: 23.2 +/- 4.6 (P < 0.05). Placebo plus GHRH: 85.4 +/- 6.9. A plus GHRH: 21.8 +/- 3.8 (P < 0.05). Mean peak GH level (microg/l) after placebo plus placebo was 5.0 +/- 1.8 not significantly different than after placebo plus A with a mean peak of 6.2 +/- 2 (P = ns). Mean peak GHRH-induced GH secretion was 26.0 +/- 15.4 and was not modified by previous A administration with mean peak of 24.4 +/- 11.8 (P = ns). CONCLUSIONS: In acromegalic patients acute pharmacological reduction of FFA with acipimox did not modify basal GH levels or GHRH-induced GH secretion, suggesting that the adenomatous somatotroph cell is unresponsive to physiological signals such as FFA which act at a pituitary level. These data support the hypothesis of an intrinsic neoplastic pituitary defect for the pathogenesis of acromegaly.

Acromegaly↗

PubMed2001

Involvement of nitric oxide in the regulation of growth hormone secretion in dogs.

Nitric oxide (NO) is a highly reactive gas that has been suggested to function as a neurotransmitter in the neuroendocrine system. In this work, we have evaluated the role of NO pathways in growth hormone (GH) secretion by assessing the effect of L-arginine infusion, a precursor of NO formation, and L-NAME, a nitric oxide synthase (NOS) inhibitor. The experiments were carried out on 7 adult beagle dogs. A saline infusion was carried out on all the dogs as a control test. L-arginine (infusion i.v. 10 g in 100 ml of saline, from t = 0 to 30 min) and L-nitro-arginine-methyl ester, L-NAME (infusion of 300 microg/kg in 120 ml of saline, from t = -30 to 45 min) were administered alone and together with growth hormone-releasing hormone (GHRH) (i.v. bolus at 0 min, at a dose of 100 microg), the synthetic GH secretagogue GHRP-6 (i.v. bolus at 0 min, at a dose of 90 microg), and the 5-HT1D serotonin receptor agonist sumatriptan, SUM (s.c. injection at the dose of 3 mg). Plasma cGH was determined by RIA. Results were evaluated by one-way analysis of variance, followed by the Newman-Keuls test for multiple comparisons. L-arginine administration resulted in a slight increase in plasma cGH in comparison with saline controls. Combined administration of L-arginine and GHRH enhanced cGH release in comparison with GHRH alone. L-NAME alone did not modify baseline cGH levels, but completely suppressed the GH release induced by GHRH or GHRP-6. It also strongly reduced, but did not abolish the effect of the two peptides (GHRH plus GHRP-6) administered together. Finally, administration of the 5-HT1D agonist SUM induced a significant cGH secretion in all dogs, a response which was not modified when L-NAME was administered in combination with SUM. In conclusion, our data show that inhibition of NO blunts both GHRH or GHRP-6-induced cGH release, and are compatible with the hypothesis that it acts by decreasing hypothalamic somatostatin release.

Animals↗

PubMed2001

Physiology and possible pathology of growth hormone secretagogues.

Growth hormone segretagogues (GHS) are artificial molecules able to stimulate growth hormone (GH) secretion. They were discovered before the hypothalamic growth hormone-releasing hormone (GHRH). These molecules had a structure devoid of opiate activity, and GHRP-6 is the most representative compound. These compounds identified a new physiological system involved in GH regulation, and their action is independent of GHRH or somatostatin. Recently an endogenous ligand for the GHS receptor, ghrelin, was discovered, suggesting that this may be the third factor in the control of GH secretion. This peptide was isolated from the stomach and is characterized by the presence of an acylated group representing a new type of molecular hormonal structure; it is able to stimulate GH secretion in vitro and in vivo in the rat. As observed for the majority of GHS, ghrelin's action is not fully specific for GH release; the acute administration of ghrelin stimulates the release of significant amounts of PRL, ACTH and cortisol. Moreover, the presence of ghrelin in rat and human placenta has been reported, suggesting a possible role of this peptide in the local modulation of GH release and in maternal and fetal pituitary secretion. Ghrelin stimulates gastric acid secretion, is able to induce adiposity by activating a central mechanism for increasing food intake and decreasing fat utilization, and ghrelin mRNA and peptide are expressed in normal and adenomatous human pituitary tissue. Possible therapeutic applications of ghrelin remain to be assessed.

Ghrelin↗

PubMed1998

Acute changes in free-fatty acids (FFA) do not alter serum leptin levels.

Leptin, the product of the ob gene, is a recently discovered hormone secreted by adipocytes. Serum leptin concentrations increase in correlation with the percentage of body fat, but besides that little is known about the physiological actions of leptin in humans. The aim of this study was to assess the influence of changes in circulating free-fatty acids on serum leptin levels. Increases in plasma FFA levels (p < 0.02) were obtained in a group of normal subjects following the administration of intralipid plus heparin (250 ml 10% Intralipid plus 5000 U heparin). FFA reduction was achieved through the administration of acipimox (250 mg, orally, at 0 min and at 210 min), a lipid-lowering drug devoid of side effects, to a group of normal (p < 0.02) and obese subjects (p < 0.05). An increase in circulating FFA levels in normal subjects (n = 6), following administration of a lipid-heparin infusion, failed to modify plasma leptin levels as assessed by the area under the curve (AUC; mean +/- SE 892 +/- 168 for placebo vs 896 +/- 260 following intralipid plus heparin). Similarly, whereas acipimox pretreatment induced a reduction in FFA levels compared to placebo in normal (n = 6) and obese subjects (n = 8), it also failed to modify plasma leptin levels at any time-point studied. The results indicate that short-term reduction or increase in circulating FFA are not associated to changes in plasma leptin levels.

Adult↗

PubMed1998

Effect of acute pharmacological reduction of plasma free fatty acids on growth hormone (GH) releasing hormone-induced GH secretion in obese adults with and without hypopituitarism.

In obesity, there is a markedly decreased GH secretion. The diagnosis of GH deficiency (GHD) in adults is based on peak GH responses to stimulation tests. In the severely obese, peak GH levels after pharmacological stimulation are often in the range that is observed in hypopituitary patients. To distinguish obese subjects from GHD patients, it will be necessary to demonstrate that reduced GH responsiveness to a given test is reversible in the former, but not in the latter, group. Recent studies have shown that reduction of plasma free fatty acids (FFA) with acipimox in obese patients restores their somatotrope responsiveness. There are no data evaluating GH responsiveness to acipimox plus GHRH in obese adults with hypopituitarism. The aim of the present study was to evaluate the effect of acute pharmacological reduction of plasma FFA on GHRH-mediated GH secretion in obese normal subjects and obese adults with hypopituitarism. Eight obese patients with a body mass index of 34.2+/-1.2; eight obese adults with hypopituitarism, with a body mass index of 35.5+/-1.9; and six control subjects were studied. All the patients showed an impaired response to an insulin-tolerance test (0.15 U/kg, i.v.), with a peak GH secretion of less than 3 microg/L. Two tests were carried out. On one day, they were given GHRH (100 microg, i.v., 0 min), preceded by placebo; and blood samples were taken every 15 min for 60 min. On the second day, they were given GHRH (100 microg, i.v., 0 min), preceded by acipimox (250 mg, orally, at -270 min and -60 min); and blood samples were taken every 15 min for 60 min. The administration of acipimox induced a FFA reduction during the entire test. Normal control subjects had a mean peak (microg/L) of 23.8+/-4.8 after GHRH-induced GH secretion; previous acipimox administration increased GHRH-induced GH secretion, with a mean peak of 54.7+/-14.5. In obese patients, GHRH-induced GH secretion was markedly reduced, with a mean peak (microg/L) of 3.9+/-1; previous administration of acipimox markedly increased GHRH-mediated GH secretion, with a mean peak of 16.0+/-3.2 (P < 0.05). In obese adults with hypopituitarism, GHRH-induced GH secretion was markedly reduced, with a mean peak (microg/L) of 2+/-0.7; previous acipimox administration did not significantly modify GHRH-mediated GH secretion, with a mean peak of 3.3+/-1.1 (P < 0.05). The GH response of obese patients and obese adults with hypopituitarism was similar after GHRH alone. In contrast, the GH response after GHRH plus acipimox, was markedly decreased in obese adults with hypopituitarism (mean peak, 3.3+/-1.1), compared with obese patients (mean peak, 16.0+/-3.2) (P < 0.05) and control subjects (mean peak, 54.7+/-14.5) (P < 0.01). In conclusion, GH secretion, after GHRH-plus-acipimox administration, is reduced in obese adults with hypopituitarism patients, when compared with obese normal patients. Testing with GHRH plus acipimox is safe and is free from side effects and could be used for the diagnosis of GHD in adults.

Adult↗

PubMed1996

Acipimox-mediated plasma free fatty acid depression per se stimulates growth hormone (GH) secretion in normal subjects and potentiates the response to other GH-releasing stimuli.

Increases in plasma free fatty acids (FFA) inhibit the GH response to a variety of stimuli; however, the role of FFA depression in GH control is far from understood. In the present work, FFA reduction was obtained by the administration to normal subjects of acipimox, a lipid-lowering drug devoid of side-effects. Each subject tested underwent two paired tests. In one, acipimox was administered orally at a dose of 250 mg at -270 min and at a dose of 250 mg at -60 min; in the matched test, placebo was given at similar intervals. To induce GH release, four stimuli acting through different mechanisms were used: pyridostigmine (120 mg, orally) at -60 min, GHRH (1 microgram/kg, iv) at 0 min, GH-releasing peptide (GHRP-6; His-D-Trp-Ala-Trp-D-Phe-Lys-NH2; 1 microgram/kg, iv) at 0 min, and finally, GHRH plus GHRP-6 at the same doses at 0 min. GH secretion was analyzed as the area under the secretory curve (AUC; mean +/- SE, micrograms per L/120 min). Acipimox pretreatment alone (n = 6) induced a reduction in FFA levels compared with placebo treatment. The FFA reduction led to a sustained GH secretion that increased from 2.4 +/- 1.8 micrograms/L at -120 min to 14.2 +/- 4.0 at 120 min. The GH AUC for placebo was 266 +/- 100, and that for acipimox was 1781 +/- 408 (P < 0.05). In the pyridostigmine-treated group (n = 6), the acipimox-pyridostigmine AUC (2046 +/- 323) was higher (P < 0.05) than the placebo-pyridostigmine AUC (764 +/- 101), but was not different from the AUC of acipimox alone. Previous FFA reduction nearly doubled the GHRH-mediated GH secretion (n = 6; placebo-GHRH AUC, 1817 +/- 365; acipimox-GHRH test, 3228 +/- 876; P < 0.05). A similar enhancement was observed when the stimulus employed was GHRP-6 (n = 6; placebo-GHRP-6 AUC, 2034 +/- 295; acipimox-GHRP-6, 4827 +/- 703; P < 0.05). Furthermore, even the most potent GH stimulus known to date, i.e. GHRH plus GHRP-6, was enhanced by the FFA suppression (placebo-GHRH-GHRP-6 AUC, 2034 +/- 277; acipimox-GHRH-GHRP-6, 5809 +/- 758; P < 0.05). The enhancing effect of lowering FFA levels was additive regardless of the stimulus employed. These results indicate that 1) FFA reduction per se stimulates GH secretion with a delayed time of action; 2) FFA reduction enhanced in an additive manner the GH secretion elicited by such different stimuli as pyridostigmine, GHRH, and GHRP-6; and 3) the observation that FFA reduction enhanced the response to the most potent GH stimulus, GHRH plus GHRP-6, suggests that FFA suppression acts by a separate mechanism. FFA reduction may have value in the clinical setting for assessing GH reserve.

Adolescent↗

PubMed1996

Impaired growth hormone secretion in obese subjects is partially reversed by acipimox-mediated plasma free fatty acid depression.

GH secretion in response to provocative stimuli is blunted in obese patients. On the other hand, increases in plasma free fatty acids (FFA) inhibit the GH response to a variety of stimuli, and FFA levels in plasma are increased with obesity. To ascertain whether FFA might be responsible for the GH secretory alterations of obesity, we studied spontaneous and stimulated GH secretion in 31 obese patients after FFA reduction by acipimox, a lipid-lowering drug devoid of serious side-effects. Each subject underwent two paired tests. In one, acipimox was administered orally at a dose of 250 mg at -270 min and at a dose of 250 mg at -60 min; in the matched test, placebo was given at similar intervals. To induce GH release, three stimuli acting through different mechanisms were used: pyridostigmine (60 mg, orally, at -60 min), GHRH (100 micrograms, iv, at 0 min), and GHRH plus GH-releasing peptide (GHRP-6; His-D-Trp-Ala-Trp-D-Phe-Lys-NH2; both at a dose of 100 micrograms, iv, at 0 min). GH secretion was analyzed as the area under the secretory curve (AUC; mean +/- SE; micrograms per L/60 min). Acipimox pretreatment alone (n = 13) induced a large reduction in FFA levels compared with placebo treatment. The FFA reduction led to a slight GH rise (AUC, 123 +/- 47), not different from that in the placebo group (61 +/- 15). In the pyridostigmine-treated group (n = 6), the acipimox-pyridostigmine AUC (408 +/- 107) was significantly higher (P < 0.05) than that in the placebo-pyridostigmine group (191 +/- 25). Furthermore, the GHRH-mediated (n = 6) AUC of GH secretion in the placebo test (221 +/- 55) was tripled by FFA reduction due to acipimox, with an AUC of (691 +/- 134; P < 0.05). Even the most potent GH stimulus known to date, i.e. GHRH plus GHRP-6, was enhanced by FFA suppression. In fact, the placebo-GHRH-GHRP-6 AUC was 1591 +/- 349, lower (P < 0.05) than that in the acipimox-GHRH-GHRP-6 test (2373 +/- 242). The enhancing effects of FFA lowering on GHRH-mediated and GHRH- plus GHRP-6-mediated GH release were synergistic. These results indicate that in obese subjects, unlike normal weight subjects. FFA reduction per se does not stimulate GH secretion. A reduction in FFA with acipimox, however, increased pyridostigmine-. GHRH-, and even GHRH- plus GHRP-6-mediated GH release, suggesting that FFA reduction operates through a different mechanism from that of these three stimuli. The abnormally high FFA levels may be a contributing factor for the disrupted GH secretory mechanisms in obesity.

Adolescent↗

PubMed1996

Growth hormone releasing hexapeptide-6 (GHRP-6) test in the diagnosis of GH-deficiency.

Pituitary GH reserve can be assessed by substances that act directly at the somatotroph, such as GHRH, or by a variety of metabolic and neuropharmacological tests acting at the hypothalamic level, such as hypoglycemia, clonidine or L-Dopa. In order to evaluate GHRP-6 as a test of pituitary GH reserve, we studied GH responses of i.v. administered GHRP-6 in a group of short-statured children, as well as in a group of adults diagnosed with growth hormone deficiency (GHD) by conventional GH testing. Although we found that the GH response to GHRP-6 was lower in patients with GHD than in normal children, on an individual basis a considerable degree of overlap was observed between the two groups. In contrast, we found an almost complete blockade of GH response to either GHRP-6 or GHRH plus GHRP-6 in patients with pituitary stalk transection, suggesting that this could be a cost-effective test for the diagnosis of this condition. A similar finding was also obtained in GH response to the combined administration of GHRH plus GHRP-6 in patients with GHD of adult onset; this test may well prove valuable in the diagnosis of this clinical entity.

Child↗

PubMed1995

Effect of combined administration of growth hormone (GH)-releasing hormone, GH-releasing peptide-6, and pyridostigmine in normal and obese subjects.

Growth hormone (GH) secretion in response to all provocative stimuli is decreased in patients with obesity. Recently, we found that the combined administration of GH-releasing hormone (GHRH) and the hexapeptide GH-releasing peptide-6 (GHRP-6) induced a large increase in plasma GH levels. To gain further insight into the disrupted mechanism of GH regulation in obesity, we investigated whether the inhibition of somatostatinergic tone with pyridostigmine could further increase the GH response to combined administration of GHRH and GHRP-6. In normal subjects, administration of GHRH plus GHRP-6 induced a marked increase in plasma GH with a peak at 30 minutes (mean +/- SEM, 76.7 +/- 9.7 micrograms/L), which was similar to that obtained after pretreatment with pyridostigmine (74.7 +/- 9.4 micrograms/L). In obese patients, combined administration of GHRH plus GHRP-6 induced a clear increase in GH secretion with a peak at 15 minutes of 42.2 +/- 10.0 micrograms/L, which was also unaffected after pretreatment with pyridostigmine (38.4 +/- 5.8 micrograms/L). The GH response was lower in obese patients than in controls as assessed by the area under the curve after administration of both GHRH plus GHRP-6 (1,846 +/- 396 v 4,773 +/- 653, P < .01) and pyridostigmine plus GHRH plus GHRP-6 (1,989 +/- 372 v 5,098 +/- 679, P < .005). In conclusion, these data suggest that GHRP-6 can behave as a functional somatostatin antagonist, and that somatotrope responsiveness to the combined administration of GHRH plus GHRP-6 is largely independent of somatostatinergic tone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Plasma growth hormone response to growth hormone-releasing hexapeptide (GH-RP-6) in children with short stature.

Eighteen children with short stature were evaluated for growth hormone (GH) reserve after pharmacological tests and a single iv injection of GH-RP-6. These children were divided into two groups: 10 were diagnosed as having idiopathic GH deficiency by classical stimulation tests (group A) and the remaining 8 (group B) were considered growth-retarded children with normal GH secretion, following conventional stimulation, but reduced endogenous GH secretion. The results were compared with a group of 12 normal children. As a group, patients in group A showed a lower GH response to GH-RP-6, while patients in group B had a similar response as normal controls. However, on an individual basis, a considerable degree of overlapping in responses among the three groups was evident. These data indicate that, on an individual basis, GH-RP-6 testing is not of diagnostic value in children suspected of having idiopathic GH deficiency.

Adolescent↗

PubMed1995

Absence of growth hormone (GH) secretion after the administration of either GH-releasing hormone (GHRH), GH-releasing peptide (GHRP-6), or GHRH plus GHRP-6 in children with neonatal pituitary stalk transection.

GH-releasing peptide (GHRP-6; His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) is a synthetic compound that releases GH in a specific and dose-related manner through mechanisms and a point of action that are mostly unknown, but different from those of GHRH. In man, GHRP-6 is more efficacious than GHRH, and a striking synergistic action occurs when both compounds are administered together. To explain such a synergistic effect, it has been postulated, but not proven, that GHRP-6 acts through a double mechanism, with actions exerted at the pituitary and the hypothalamic level. On the other hand, patients with the syndrome of GH deficiency due to perinatal pituitary stalk transection have any hypothalamic factor nonoperandi. The aim of the present study was 3-fold: 1) to further understand how relevant, if at all, the hypothalamic action of GHRP-6 is for GH regulation; 2) to evaluate whether GHRP-6 plus GHRH could be a suitable diagnostic tool in children with pituitary stalk transection; and 3) to compare these results with similar published studies performed in patients with hypothalamo-pituitary disconnection, who developed the disease as adults. Seven patients with GH deficiency and different degrees of panhypopituitarism due to perinatal pituitary stalk transection and 7 age- and sex-matched normal controls were studied. The subjects underwent 3 different tests on separate occasions, being challenged with GHRH (1 microgram/kg, iv), GHRP-6 (1 microgram/kg, iv), or GHRH plus GHRP-6. GH was analyzed as the area under the curve (mean +/- SE; micrograms per L/90 min). In normal subjects, GH secretion was 1029 +/- 202 after GHRH treatment, 1221 +/- 345 after GHRP-6, and 3542 +/- 650 after GHRH plus GHRP-6; the latter value was significantly (P < 0.05) higher than the secretion elicited by GHRH or GHRP-6 alone. In the group of patients with perinatal pituitary stalk transection, the level of GH after GHRH treatment was 116 +/- 22 and was even more reduced (P < 0.05) after GHRP-6 treatment (37 +/- 8). After GHRH plus GHRP-6, GH secretion in those patients was 177 +/- 27, significantly higher (P < 0.05) than the secretion induced by either GHRH or GHRP-6 alone. Individually examined, none of the patients tested with the most potent stimulus known to date (GHRH plus GHRP-6) exhibited GH secretion greater than 5 micrograms/L.(ABSTRACT TRUNCATED AT 400 WORDS)

Child↗

PubMed1995

Role of the serotonin receptor subtype 5-HT1D on basal and stimulated growth hormone secretion.

At present, four main types of serotonin (5-HT) receptors have been identified in the brain (5-HT1, 5-HT2, 5-HT3, and 5-HT4). In addition, the 5-HT1 have been further subclassified. We have taken advantage of a new selective 5-HT1D receptor agonist 3-[2-(dimethylamino)ethyl]-N-methyl-1H-indole-5-methanesulfonamide succinate, Sumatriptan, to evaluate the role of 5-HT1D receptors on GH secretion. To this end, several tests with or without sumatriptan were undertaken in normal prepubertal children. Furthermore, we assessed the effect of Sumatriptan on basal GH secretion and the GH response to GHRH in obese children. In normal children, Sumatriptan administration (3 mg, sc) resulted in an increase in basal GH levels at 30 min (7.7 +/- 1.5 micrograms/L; P < 0.05) and increased GH responses to GHRH (47.3 +/- 6.4 vs. 29.6 +/- 9.7 micrograms/L; P < 0.05). The Sumatriptan-induced increase in GH responses to GHRH was dependent on the stimulus tested. Pretreatment with Sumatriptan did not modify the GH response to clonidine or pyridostigmine, as assessed by the peak GH response and the area under the curve. In contrast, it increased the GH response to arginine. In the obese subjects, the GH response to GHRH was reduced (7.3 +/- 1.0 vs. 29.6 +/- 9.7 micrograms/L at 30 min) compared to that in control children (P < 0.05). Sumatriptan administration did not alter the basal GH value (peak GH, 1.7 +/- 0.3 micrograms/L at 30 min). However, Sumatriptan administration clearly increased the effect of GHRH, resulting in a GH peak of 14.6 +/- 3.1 micrograms/L at 30 min (P < 0.01). To assess the specificity of Sumatriptan on anterior pituitary hormone secretion, we studied its effect on TSH and PRL responses to TRH as well as LH-releasing hormone-induced LH and FSH secretion. Administration of Sumatriptan did not alter the response of any of these hormones. Our results indicate that 5-HT1D receptors have a stimulatory effect on GH secretion, possibly by inhibiting hypothalamic somatostatin release.

Arginine↗

PubMed1993

Influence of sex, age and adrenergic pathways on the growth hormone response to GHRP-6.

OBJECTIVE: His-dTrp-Ala-Trp-dPhe-Lys-NH2 (GHRP-6) is a synthetic compound that releases GH in a dose-related and specific manner in several species including man. To further characterize the effects of GHRP-6 on GH secretion in normal human subjects, we assessed plasma GH levels following GHRP-6 administration in normal male adult subjects, normal female adult subjects at different stages of their menstrual cycle and in normal prepubertal male and female children. We also studied the influence of adrenergic pathways on GHRP-6 induced GH secretion in normal adult male subjects. DESIGN: In a group of eight volunteers the following tests were carried out: GHRP-6 alone (1 microgram/kg i.v. at 0 minutes); propranolol (40 mg p.o. at -30 minutes) plus GHRP-6; and prazosin (3 mg p.o. at -120 minutes) plus GHRP-6. Another group of eight volunteers were studied with GHRP-6 as above; clonidine alone (300 mg p.o. at -60 minutes); and clonidine plus GHRP-6. A group of nine women were studied with 1 microgram/kg i.v. of GHRP-6 at 0 minutes, at different stages of their menstrual cycle. Finally, 12 children were studied with GHRP-6 using the same dose and methods as above. PATIENTS: Twenty-five normal adult subjects (16 male and nine female) and 12 normal prepubertal children (six male and six female) wer studied after giving informed consent. MEASUREMENTS: Plasma GH levels were measured by radioimmunoassay. RESULTS: No differences in GH responses to GHRP-6 were found between children and normal adult male or female subjects at different stages of their menstrual cycle. Administration of propranolol and clonidine did not modify the GH responses to GHRP-6 in male adults. In contrast, prazosin administration induced an increase in plasma GH levels that was statistically different from that of GHRP-6 alone (. < 0.05 between area under curve). CONCLUSIONS: GHRP-6 exerts a potent stimulatory effect on GH secretion in adults and children. Its effects, at least at the dose studied, are independent of sex and age. Noradrenergic pathways through alpha 2 adrenergic receptors are unlikely to influence this response.

Adult↗

PubMed1993

Effect of growth hormone (GH)-releasing hormone (GHRH), atropine, pyridostigmine, or hypoglycemia on GHRP-6-induced GH secretion in man.

His-DTrp-Ala-Trp-DPhe-Lys-NH2 (GHRP-6) is a synthetic compound that releases GH in a dose-related and specific manner in several species, including man. To further characterize the effects and mechanism of action of GHRP-6 on GH secretion, we assessed in normal man plasma GH responses to that hexapeptide 1) alone and in combination with exogenous GH-releasing hormone (GHRH) administration, 2) in a state of high endogenous somatostatinergic tone after atropine administration, and 3) in a state of low endogenous somatostatinergic tone induced by the cholinergic receptor agonist drug pyridostigmine or after insulin-induced hypoglycemia. We found a similar increase in plasma GH levels after the administration of either GHRP-6 (1 microgram/kg) or GHRH (1 microgram/kg); the areas under the curve (AUC) were (mean +/- SEM) 973 +/- 181 and 821 +/- 139, respectively. After combined GHRP-6 and GHRH administration, GH responses were considerably greater than those after either compound alone (4412 +/- 842; P < 0.01). Administration of the cholinergic receptor antagonist atropine (1 mg, im) completely prevented the GH responses to GHRP-6 (area under the curve, 103 +/- 14 vs. 815 +/- 156, respectively). On the other hand, pyridostigmine, a cholinergic agonist, slightly increased GH responses to GHRP-6 (P < 0.01 when comparing the AUC after pyridostigmine administration of 1571 +/- 151 and the AUC after administration of GHRP-6 alone of 815 +/- 156). Finally, combined GHRP-6 and insulin administration induced a much greater increase in plasma GH levels (AUC, 4047 +/- 327) than insulin alone (1747 +/- 229; P < 0.05) or GHRP-6 alone (1248 +/- 376; P < 0.05). Our results lend support to the view that GHRP-6-induced GH secretion is exerted through a non-GHRH-dependent mechanism. Furthermore, the fact that enhancement of somatostatinergic tone with atropine completely prevented the GH responses to GHRP-6, while pyridostigmine and insulin-induced hypoglycemia, which increased plasma GH levels by inhibiting hypothalamic somatostatin release, increased the same response suggest that although GHRP-6-induced GH secretion is dependent on the endogenous somatostatinergic tone, the stimulatory effect of GHRP-6 on plasma GH levels is not mediated by a change in hypothalamic somatostatinergic tone.

Adult↗

PubMed1993

Massive growth hormone (GH) discharge in obese subjects after the combined administration of GH-releasing hormone and GHRP-6: evidence for a marked somatotroph secretory capability in obesity.

GH secretion in response to all provocative stimuli is decreased in patients with obesity. However, the precise mechanism causing this impairment in GH release is unknown. His-DTrp-Ala-Trp-DPhe-Lys-NH2 (GHRP-6) is a synthetic compound that releases GH in a dose-related and specific manner in several species, including man. To gain further insight into disrupted GH secretion in obesity, GHRP-6 and GH-releasing hormone (GHRH) at a dose of 100 micrograms, i.v., were administered either alone or in combination in a group of 19 obese subjects. In a group of obese patients, GHRP-6 induced GH secretion, with a GH peak (mean +/- SEM) of 15.7 +/- 4.4 micrograms/L and an area under the curve (AUC) of 674 +/- 187, which were larger than those after GHRH stimulation (6.8 +/- 1.1 and 412 +/- 71, respectively). Enhancement of the endogenous cholinergic tone was obtained in another group of obese subjects by means of pyridostigmine (120 mg, orally). Pyridostigmine administered 60 min before GHRP-6, increased both the mean GH peak (32.2 +/- 6.9) and the AUC (1413 +/- 537) after GHRP-6 administration. In a separate group of subjects, the combined administration of GHRP-6 and GHRH induced a massive discharge of GH, with individual responses ranging from 14-86 micrograms/L. GHRP-6 plus GHRH induced a mean GH peak of 42.2 +/- 10.9 and an AUC of 1894 +/- 784 (P < 0.05), clearly indicating a potentiating (synergic) action when the two compounds were administered together. These data show that GH responses to GHRP-6 were almost twice those to GHRH in obese patients. The stimulatory effect exerted by pyridostigmine on GHRP-6-induced GH secretion supported the view of increased somatostatinergic tone in obesity. Finally, the massive GH discharge that followed the administration of GHRH plus GHRP-6 was not observed after any stimulus in obesity, clearly indicating that the impaired GH secretion is a functional and potentially reversible state.

Adolescent↗

PubMed1993

Influence of endogenous cholinergic tone and alpha-adrenergic pathways on growth hormone responses to His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 in the dog.

His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6) is a synthetic peptide unrelated to any known hypothalamic-releasing hormone including growth hormone-releasing hormone (GHRH). Interestingly, this peptide induces a dose-related increase in plasma GH levels in all species tested so far. The aim of this study was to investigate the action of GHRP-6 alone or in combination with GHRH on GH release in dogs. In addition, the activation or blockade of endogenous cholinergic tone and alpha-1 adrenoceptors on GHRP-6-stimulated GH secretion was assessed. In adult Beagle dogs (n = 10), GHRP-6 (90 micrograms i.v.) increased basal GH levels from 2.6 +/- 1.5 to 14.4 +/- 3.1 micrograms/l (mean +/- S.E.M.) after 15 min. GHRH (50 micrograms i.v.) induced a GH peak of 9.7 +/- 2.2 micrograms/l at 15 min. The combined administration of GHRP-6 and GHRH strikingly potentiated canine GH release with a peak of 54 +/- 9.0 micrograms/l (P < 0.01). Pretreatment with the cholinergic agonist pyridostigmine (30 mg per os) increased GHRP-6-stimulated GH secretion (37.9 +/- 10.1 micrograms/l P < 0.05), while the muscarinic blocker atropine (100 micrograms i.v.) completely abolished (GH peak lower than 2 micrograms/l) the stimulatory action of GHRP-6. On the other hand, administration of the alpha-2 adrenergic agonist clonidine (4 micrograms/kg i.v.) increased basal plasma GH levels without affecting GH responses to GHRP-6.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Role of cholinergic muscarinic pathways on the free fatty acid inhibition of GH responses to GHRH in normal men.

In order to explore the mechanisms by which free fatty acids (FFA) inhibit GH secretion, we studied the effect of the acetylcholinesterase inhibitor pyridostigmine (120 mg p.o.) on the FFA blockade of GH responses to the administration of GHRH (100 micrograms i.v.) in seven normal subjects. GHRH-induced GH secretion was significantly reduced following elevation of circulating FFA levels by lipid-heparin infusion and significantly potentiated by previous pyridostigmine treatment. Peak GH levels following combined administration of pyridostigmine plus lipid-heparin plus GHRH were significantly higher (P less than 0.01) than after GHRH alone and significantly lower than after pyridostigmine plus GHRH (P less than 0.01). In conclusion, central cholinergic activation by pyridostigmine, with the presumed reduction in somatostatin discharge, reversed the blocking effect of FFA on GHRH-stimulated GH release. Conversely, FFA were able to reduce even a maximal GH stimulation by pyridostigmine plus GHRH.

Adult↗