Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Growth hormone-releasing peptide 6 (GHRP-6) is a synthetic hexapeptide with a potent GH-releasing activity after intravenous, subcutaneous, intranasal and oral administration in man. Previous data showed its activity also in some patients with GH deficiency. The aim of our study was to verify the GH-releasing activity of oral GHRP-6 administration on GH secretion in children with normal short stature. The effect of oral GHRP-6 (300 micrograms/kg) was compared with that of the maximally effective dose of intravenous GH-releasing hormone (GHRH-29, 1 microgram/kg). As the GHRH-induced GH rise in children is potentiated by arginine (ARG), even when administered by oral route at low dose (4 g), we studied also the interaction of oral GHRP-6 and ARG administration. We studied 13 children (nine boys and four girls aged 6.2-10.5 years, pubertal stage I) with normal short stature (height less than -2 SD score; height velocity more than -2 SD score; normal bone age; insulin-like growth factor I > 70 micrograms/l). In a first group of children (N = 7), oral GHRP-6 administration induced a GH response (mean +/- SEM; peak at 60 min vs baseline: 18.8 +/- 3.0 vs 1.1 +/- 0.3 micrograms/l, p < 0.0006; area under curve: 1527.3 +/- 263.9 micrograms l-1 h-1) which was similar to that elicited by GHRH (peak at 45 min vs baseline: 20.8 +/- 4.5 vs 2.2 +/- 0.9 micrograms/l, p < 0.007; area under curve: 1429.4 +/- 248.2 micrograms l-1 h-1).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth hormone-releasing effect of oral growth hormone-releasing peptide 6 (GHRP-6) administration in children with short stature. 758 65

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)
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PMID:Effect of combined administration of growth hormone (GH)-releasing hormone, GH-releasing peptide-6, and pyridostigmine in normal and obese subjects. 778 58

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.
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PMID:Effect of growth hormone (GH)-releasing hormone (GHRH), atropine, pyridostigmine, or hypoglycemia on GHRP-6-induced GH secretion in man. 842 Oct 84

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.
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PMID: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. 847 88

This study was conducted to determine the effects of acute and chronic administration of GH-releasing peptide-2 (D-Ala-D-beta Nal-Ala-Trp-D-Phe-Lys-NH2, GHRP-2 or KP102) on GH responsiveness in male Holstein calves. In the dose response study of acute administration, six calves were injected iv with saline or 6.25, 12.5 and 25.0 micrograms/kg body weight (BW) of KP102. The GH AUC (area under curve, ng/ml.min, mean +/- SEM) for 60 min was significantly increased with 6.25 (676.3 +/- 125.6), 12.5 (1574.8 +/- 318.0) and 25.0 (1578.7 +/- 214.6) micrograms/kgBW of KP102 than with saline (78.6 +/- 36.1) (P < 0.01). GH responses were decreased by multiple injections of 12.5 micrograms/kgBW KP102 at every 2 h for 8 h. The GH AUC for 60 min was decreased from the first injection (1162.9 +/- 313.3) to the second injection (604.7 +/- 131.9), but the response was significantly higher for the first and second injections than the third (304.4 +/- 173.1) and fourth injections (320.7 +/- 144.2) (P < 0.05). In the chronic administration, 8 calves were implanted subcutaneously with osmotic pumps (Alzet pump). Each of the 4 calves was given with 12.5 micrograms/kgBW per hour KP102 and the other 4 calves served as the control. During the 14 day period, average daily gain was significantly increased (36.4%) over the control (P < 0.05). Food efficiency was not significant, but numerically higher (29.4%) than the control. The plasma GH concentration was not increased by chronic administration of KP102, but IGF-I appeared to increase in KP102-treated calves more than the control. These results suggest that the synthetic KP102 can be used for enhancing the growth performance in domestic animals.
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PMID:Characteristics of growth hormone secretion responsiveness to growth hormone-releasing peptide-2 (GHRP-2 or KP102) in calves. 888 23

In this study we investigated the neurochemical identity of the arcuate cells activated following GH-releasing peptide-6 (GHRP-6) injection by comparing, on consecutive sections, the distribution c-fos messenger RNA (mRNA) with that of mRNAs for peptides synthesized in arcuate cells, including neuropeptide Y (NPY), GH-releasing factor (GRF), tyrosine hydroxylase, POMC, and somatostatin. Rats bearing chronically implanted jugular catheters were injected with either 50 micrograms GHRP-6 or vehicle. Thirty minutes later they were terminally anesthetized and perfused with fixative. Paraffin-embedded sections of 7 microns thickness were processed using in situ hybridization for either c-fos mRNA or mRNAs for the neurochemical markers. In GHRP-6-treated rats the mean (+/-SEM) number of cells expressing c-fos mRNA in the arcuate nucleus (23 +/- 2 cells/section per rat; n = 5) was significantly higher than for vehicle-treated controls (2 +/- 1 cells/section per rat; n = 5; P < 0.001, Mann-Whitney U test). Superimposed camera lucida maps indicated that, in GHRP-6-injected rats, neurochemically identifiable cells expressing c-fos mRNA also express NPY mRNA (51 +/- 4%), GRF mRNA (23 +/- 1%) tyrosine hydroxylase mRNA (11 +/- 3%), POMC mRNA (11 +/- 2%), or somatostatin mRNA (4 +/- 1%). Thus, the majority of cells expressing c-fos mRNA following GHRP-6 injection are NPY and GRF-containing cells.
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PMID:Induction of c-fos messenger ribonucleic acid in neuropeptide Y and growth hormone (GH)-releasing factor neurons in the rat arcuate nucleus following systemic injection of the GH secretagogue, GH-releasing peptide-6. 900 14

Prolonged critical illness is characterized by protein hypercatabolism and preservation of fat depots, associated with blunted GH secretion, elevated serum cortisol levels, and low insulin-like growth factor I (IGF-I) concentrations. In this condition, GH is readily released in response to a bolus of GHRH and GH-releasing peptide-2 (GHRP-2) and, paradoxically, to TRH. We further explored the altered somatotropic axis and cortisol secretion in critical illness by examining the effects of continuous GHRH and/or GHRP-2 infusion. Twenty-six critically ill adults (mean age +/- SEM, 63 +/- 2 yr) were studied during 2 consecutive nights (2100-0600 h). According to a weighed randomization, they received one of four combinations of infusions within a randomized cross-over design for each combination: placebo (one night) and GHRP-2 (the other night; n = 10), placebo and GHRH (n = 4), GHRH and GHRP-2 (n = 6), and GHRP-2 and GHRH plus GHRP-2 (n = 6). The peptide infusions (duration, 21 h) were started after a bolus of 1 microgram/kg at 0900 h and infused (1 microgram/kg/h) until 0600 h. Serum concentrations of GH were determined every 20 min, cortisol every hour, and IGF-I at 2100 and 0600 h on each study night. The placebo profiles showed pulsatile GH secretion with low secretory burst amplitude [0.062 +/- 0.008 microgram/L distribution volume (Lv)/min], high burst frequency (6.6 +/- 0.4 events/9 h), and detectable basal secretion (0.041 +/- 0.009 microgram/L/min) in the face of low serum IGF-I (106 +/- 11 micrograms/L). IGF-I correlated positively and significantly with the basal component, the pulsatile component, and the total amount of nightly GH secretion. GHRH elicited a 2- to 3-fold increase in the mean GH concentration (P = 0.006), the GH secretory burst amplitude (P = 0.007), and basal GH secretion (P = 0.03). GHRP-2 provoked a 4- to 6-fold increase in the mean GH concentration (P < 0.0001), the GH secretory burst amplitude (P = 0.002), and basal GH secretion (P = 0.0007), which were associated with a 61 +/- 13% increase in serum IGF-I within 24 h (P = 0.02). Compared to GHRP-2 alone, GHRH plus GHRP-2 elicited a further 2-fold increase in the mean GH concentration (P = 0.04) and GH basal secretion (P = 0.02), and an additional 40 +/- 6% rise in serum IGF-I (P = 0.04). GHRH and GHRP-2 infusion did not alter elevated cortisol levels. In critically ill adults, low serum IGF-I levels were positively correlated with diminished pulsatile and increased basal GH secretion. Both basal and pulsatile GH secretion were moderately increased by continuous infusion of GHRH, substantially increased by GHRP-2, and strikingly increased by GHRH plus GHRP-2. GHRP-2 alone or combined with GHRH elicited a robust rise in circulating IGF-I levels within 24 h without altering serum cortisol levels. These findings open perspectives for GH secretagogues as potential antagonists of the catabolic state in critical care medicine.
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PMID:The somatotropic axis in critical illness: effect of continuous growth hormone (GH)-releasing hormone and GH-releasing peptide-2 infusion. 902 60

A diagnostic test was devised to evaluate pituitary growth hormone (GH) secretory potential. GH secretory dynamics were assessed in children with and without GH deficiency. The GH response was measured to GH-releasing hormone (GHRH) and the GH-releasing peptide GHRP-2, administered sequentially. The mean (+/- SEM) peak GH response to GHRP-2 was 20.1 +/- 5.5, 63.6 +/- 24.9 and 42.2 +/- 4.3 micrograms/l for GH-deficient, slowly growing non-GH-deficient and control children, respectively (p < 0.02 and p < 0.05 for GH-deficient vs controls and slowly growing children, respectively). Corresponding values for area under the curve (AUC) were 995 +/- 371. 2460 +/- 953 and 1598 +/- 274 micrograms/l x minute. Peak GH (and AUC) responses to GHRH were 19.6 +/- 5.1 micrograms/l (924 +/- 232 micrograms/l x minute), 31.4 +/- 8.4 micrograms/l (1544 +/- 449 micrograms/l x minute) and 39.8 +/- 7.8 micrograms/l (2201 +/- 437 micrograms/l x minute) for the same three groups, respectively (p < 0.05 for peak GH in GH-deficient patients vs controls, and p < 0.02 and p < 0.01 for AUC in GH-deficient vs slowly growing children and controls, respectively). The ratio of the peak GH response to GHRP-2 and GHRH was similar in all three groups. As these secretagogues stimulate different aspects of hypothalamic function (i.e., they are functional complements), robust GH secretion in response to GHRH or GHRP could suggest adequate endogenous GHRP or GHRH, respectively. A poor response to either GH secretagogue administered individually could represent inadequacy of its endogenous complement. The integrity of functional pituitary elements could be differentiated from inadequate complements by administering both GH secretagogues simultaneously. Application of these principles should allow a better definition of the underlying disorder and provide the basis for therapeutic strategies for those patients with abnormal GH production and/or secretion.
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PMID:Growth hormone secretagogues in children with altered growth. 940 54

GH-releasing peptide-6 (GHRP-6) is a potent GH secretagogue that releases GH by uncertain mechanisms. To assess whether GHRH is required for GH release by GHRP-6 in humans, we used the specific antagonist to GHRH (N-Ac-Tyr1,D-Arg2)GHRH(1-29)NH2 (GHRH Ant). We have previously shown that GHRH-Ant (400 microg/kg) blocked the GH response to 0.33 and 3.3 microg/kg boluses of GHRH by 95% and 81%, respectively. Nine healthy men between the ages of 20 and 30 yr were studied on two occasions. They received either saline or GHRH-Ant (400 microg/kg, i.v.) at 0840 h, followed by GHRP-6 (1 microg/kg, i.v. bolus) at 0900 h. Blood was sampled every 10 min from 0800-1100 h. GH responses were measured as the maximal increase over the baseline GH concentration and as the area under the curve. GHRH-Ant eliminated most of the GH response to GHRP-6 [maximal increase over the baseline GH concentration, 33.8 +/- 4.8 vs. 6.2 +/- 1.8 microg/L (mean +/- SEM; P < 0.0001); area under the curve, 1701 +/- 278 vs. 376 +/- 113 microg/min x L (P < 0.001)]. These data show that endogenous GHRH is necessary for most of the GH response to GHRP-6 in humans.
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PMID:Growth hormone (GH)-releasing peptide-6 requires endogenous hypothalamic GH-releasing hormone for maximal GH stimulation. 1129 68

Hexarelin (HEX) is a synthetic GHRP which acts on specific receptors at both the pituitary and the hypothalamic level to stimulate GH release both in animals and in humans. Like other GHRPs, HEX possesses also acute ACTH and cortisol-releasing activity similar to that of hCRH. The mechanisms underlying the stimulatory effect of GHRPs on hypothalamo-pituitary-adrenal (HPA) axis are still unclear, although a CNS-mediated action has been demonstrated. In 6 normal healthy young women (26-34 years) we studied the effects on ACTH and cortisol secretion of HEX (2.0 microg/kg i.v. at 0 min) alone and preceded by dexamethasone (DEXA, 1 mg p.o. at 23.00 h on the previous night) or alprazolam (ALP, 0.02 mg/kg p.o. at -90 min), a benzodiazepine which binds to GABA receptors and possesses CRH-mediated inhibitory activity on HPA axis. ACTH and cortisol secretion after saline administration as well as the GH response to HEX alone and preceded by DEXA or ALP were also studied. HEX administration elicited an increase in ACTH (peak vs. baseline, mean +/- SEM: 28.0 +/- 6.7 vs. 11.7 +/- 2.2 pg/ml, p < 0.05) and cortisol secretion (162.6 +/- 15.0 vs. 137.7 +/- 12.6 microg/l, p < 0.05). DEXA pretreatment strongly inhibited basal ACTH (3.2 +/- 0.7 pg/ml, p < 0.01) and cortisol levels (11.3 +/- 2.5 microg/l, p < 0.001) and abolished the ACTH and cortisol responses to HEX (3.6 +/- 0.9 pg/ml, p < 0.01 and 10.7 +/- 2.0 microg/l, p < 0.001), respectively. On the other hand, ALP pretreatment did not significantly modify basal ACTH (7.9 +/- 2.0 pg/ml) and cortisol levels (127.6 +/- 14.5 microg/l) but abolished the HEX-induced ACTH and cortisol secretions (8.6 +/- 2.4 pg/ml, p < 0.05 and 111.0 +/- 6.0 microg/l, p < 0.05), respectively. ACTH and cortisol levels after HEX when preceded by ALP overlapped with those recorded during saline. HEX induced a clear GH response (peak at 15 min vs. baseline: 65.5 +/- 20.5 vs. 2.2 +/- 0.7 microg/l, p < 0.03) which was blunted by ALP (peak at 15 min: 21.5 +/- 5.5 microg/l, p < 0.05) while it was not modified by DEXA pretreatment (78.7 +/- 7.6 microg/l). In conclusion, our present data demonstrate that the ACTH- and cortisol-releasing effect of HEX is abolished by either dexamethasone or alprazolam, a benzodiazepine, which is even able to blunt the GH-releasing activity of the hexapeptide. These findings suggest that, in physiological conditions, the stimulatory effect of GHRPs on HPA axis is sensitive to the negative glucocorticoid feedback and could be mediated by GABAergic mechanisms; the latter seem also involved in the GH-releasing activity of GHRPs.
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PMID:Effects of dexamethasone and alprazolam, a benzodiazepine, on the stimulatory effect of hexarelin, a synthetic GHRP, on ACTH, cortisol and GH secretion in humans. 964 12


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