Biomedical subjects

Fabio Broglio

Publications and source records attributed to Fabio Broglio.

32 records · Page 2Linked to original sources

PubMed2003

Ghrelin and the endocrine pancreas.

Ghrelin is a 28-amino-acid peptide predominantly produced by the stomach, while substantially lower amounts derive from other tissues including the pancreas. It is a natural ligand of the GH secretagogue (GHS) receptor (GHS-R1a) and strongly stimulates GH secretion, but acylation in serine 3 is needed for its activity. Ghrelin also possesses other endocrine and nonendocrine actions reflecting central and peripheral GHS-R distribution including the pancreas. The wide spectrum of ghrelin activities includes orexigenic effect, control of energy expenditure, and peripheral gastroenteropancreatic actions. Circulating ghrelin levels mostly reflect gastric secretion as indicated by evidence that they are reduced by 80% after gastrectomy and even after gastric by-pass surgery. Ghrelin secretion is increased in anorexia and cachexia but reduced in obesity, a notable exception being Prader-Willi syndrome. The negative association between ghrelin secretion and body weight is emphasized by evidence that weight increase and decrease reduces and augments circulating ghrelin levels in anorexia and obesity, respectively, and agrees with the clear negative association between ghrelin and insulin levels. In fact, ghrelin secretion is increased by fasting whereas it is decreased by glucose load as well as during euglycemic clamp but not after arginine or free fatty acid load in normal subjects; in physiological conditions, however, the most remarkable inhibitory input on ghrelin secretion is represented by somatostatin as well as by its natural analog cortistatin that concomitantly reduce beta-cell secretion. This evidence indicates that the endocrine pancreas plays a role in directly or indirectly modulating ghrelin secretion.

Animals↗

PubMed2002

Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT.

Ghrelin is an acyl-peptide gastric hormone acting on the pituitary and hypothalamus to stimulate growth hormone (GH) release, adiposity, and appetite. Ghrelin endocrine activities are entirely dependent on its acylation and are mediated by GH secretagogue (GHS) receptor (GHSR)-1a, a G protein-coupled receptor mostly expressed in the pituitary and hypothalamus, previously identified as the receptor for a group of synthetic molecules featuring GH secretagogue (GHS) activity. Des-acyl ghrelin, which is far more abundant than ghrelin, does not bind GHSR-1a, is devoid of any endocrine activity, and its function is currently unknown. Ghrelin, which is expressed in heart, albeit at a much lower level than in the stomach, also exerts a cardio protective effect through an unknown mechanism, independent of GH release. Here we show that both ghrelin and des-acyl ghrelin inhibit apoptosis of primary adult and H9c2 cardiomyocytes and endothelial cells in vitro through activation of extracellular signal-regulated kinase-1/2 and Akt serine kinases. In addition, ghrelin and des-acyl ghrelin recognize common high affinity binding sites on H9c2 cardiomyocytes, which do not express GHSR-1a. Finally, both MK-0677 and hexarelin, a nonpeptidyl and a peptidyl synthetic GHS, respectively, recognize the common ghrelin and des-acyl ghrelin binding sites, inhibit cell death, and activate MAPK and Akt.These findings provide the first evidence that, independent of its acylation, ghrelin gene product may act as a survival factor directly on the cardiovascular system through binding to a novel, yet to be identified receptor, which is distinct from GHSR-1a.

Animals↗

PubMed2002

Effects of acute hexarelin administration on cardiac performance in patients with coronary artery disease during by-pass surgery.

Growth hormone (GH) secretagogues are synthetic molecules with neuroendocrine but also cardiovascular activities mediated by specific GH secretagogue-receptors. The acute administration of hexarelin, a peptidyl GH secretagogue, increases left ventricular ejection fraction in normal subjects and even in patients with severe GH deficiency. We evaluated cardiac performances in patients with coronary artery disease after acute administration of hexarelin (2.0 microg/kg, i.v.) compared to that in patients given with GH-releasing hormone (GHRH; 2.0 microg/kg, i.v.), recombinant human (rh)-GH (10.0 microg/kg, i.v.) or placebo. Cardiac performance was studied in 24 male patients (age [mean +/- S.E.M.]: 59.5 +/- 1.1 years; body mass index: 24.6 +/- 0.9 kg/m(2); left ventricular ejection fraction: 57.2 +/- 1.4%) with coronary artery disease undergoing by-pass surgery during general anesthesia. Left ventricular ejection fraction, left ventricular end diastolic volume, cardiac index and cardiac output were evaluated by intraoperative omniplane transoesophageal echocardiography while wedge pressure, central venous pressure, mean arterial pressure and systemic vascular resistance index were evaluated by systemic and pulmonary arterial catheterization. RhGH, GHRH and placebo did not exert any hemodynamic effect while hexarelin induced a prompt (after +10 min) increase in left ventricular ejection fraction (P < 0.001), cardiac index (P < 0.001) and cardiac output (P < 0.001) lasting up to +90 min without any variation in left ventricular end diastolic volume. Accordingly, hexarelin induced a reduction of wedge pressure (P < 0.01). These changes occurred in the presence of increased mean arterial pressure (P < 0.05) and transient decrease of central venous pressure (P < 0.05 at +30 min only) but no change in systemic vascular resistance index. Heart rate after hexarelin was similar to that after placebo. Hexarelin induced a slight increase in GH levels which was similar to that after GHRH but far lower (P < 0.01) than that after rhGH. Thus, in patients with coronary artery disease undergoing by-pass surgery, the acute administration of hexarelin clearly improves cardiac performance without any relevant variation in systemic vascular resistance. The cardiotropic effect of hexarelin is not shared by GHRH or by rhGH, indicating that it is not mediated by the increase in circulating GH levels but more likely reflects activation of specific cardiovascular GH secretagogue receptors.

Analysis of Variance↗

PubMed2002

The GH-releasing effect of ghrelin, a natural GH secretagogue, is only blunted by the infusion of exogenous somatostatin in humans.

OBJECTIVE: Ghrelin, a 28-amino-acid peptide purified from the stomach and showing a unique structure with an n-octanoyl ester at the serine 3 residue, is a natural ligand of the GH secretagogue (GHS) receptor (GHS-R). Ghrelin strongly stimulates GH secretion in both animals and humans, showing a synergistic effect with GH-releasing hormone (GHRH) but no interaction with synthetic GHS. However, the activity of ghrelin as well as that of non-natural GHS is not fully specific for GH; ghrelin also induces a stimulatory effect on lactotroph and corticotroph secretion, at least in humans. DESIGN: To further clarify the mechanisms underlying the GH-releasing activity of this natural GHS, we studied the effects of somatostatin (SS, 2.0 microg/kg/h from -30 to +90 min) on the endocrine responses to ghrelin (1.0 microg/kg i.v. at 0 min) in seven normal young male volunteers [age (mean +/- SEM) 28.6 +/- 2.9 years; body mass index (BMI) 22.1 +/- 0.8 kg/m2]. In the same subjects, the effect of SS on the GH response to GHRH (1.0 microm/kg i.v. at 0 min) was also studied. MEASUREMENTS: Blood samples were taken every 15 min from -30 up to +120 min. GH levels were assayed at each time point in all sessions; PRL, ACTH and cortisol levels were assayed after ghrelin administration alone and during SS infusion. RESULTS: The GH response to ghrelin (hAUC0'-->120' 2695.0 +/- 492.6 microg min/l) was higher (P < 0.01) than that after GHRH (757.1 +/- 44.1 microg min/l). SS infusion almost abolished the GH response to GHRH (177.0 +/- 37.7 microg min/l, P < 0.01); the GH response to ghrelin was inhibited by SS (993.8 +/- 248.5 microg min/l, P < 0.01) but GH levels remained higher (P < 0.05) than with GHRH. Ghrelin induced significant increases in PRL, ACTH and cortisol levels and these responses were not modified by SS. CONCLUSIONS: Ghrelin, a natural GHS-R ligand, exerts a strong stimulatory effect on GH secretion in humans and this effect is only blunted by an exogenous somatostatin dose which almost abolishes the GH response to GHRH. The stimulatory effect of ghrelin on lactotroph and corticotroph secretion is refractory to exogenous somatostatin, indicating that these effects occur through pathways independent of somatostatinergic influence.

Adrenocorticotropic Hormone↗

PubMed2002

Endocrine responses to ghrelin in adult patients with isolated childhood-onset growth hormone deficiency.

OBJECTIVE: Ghrelin, a 28 amino acid acylated peptide, is a natural ligand of the GH secretagogues (GHS) receptor (GHS-R), which is specific for synthetic GHS. Similar to synthetic GHS, ghrelin strongly stimulates GH secretion but also displays significant stimulatory effects on lactotroph and corticotroph secretion. It has been hypothesized that isolated GH deficiency (GHD) could reflect hypothalamic impairment that would theoretically involve defect in ghrelin activity. PATIENTS: In the present study, we verified the effects of ghrelin (1 microg/kg i.v.) on GH, PRL, ACTH and cortisol levels in adult patients with isolated severe GHD [five males and one female, age (mean +/- SEM) 24.7 +/- 2.6 years, BMI 25.7 +/- 2.7 kg/m2]. In all patients, the GH response to insulin-induced hypoglycaemia (ITT, 0.1 IU regular insulin i.v.) and GH releasing hormone (GHRH) (1 microg/kg i.v.) + arginine (ARG, 0.5 g/kg i.v.) was also studied. The hormonal responses in GHD were compared with those in age-matched normal subjects (NS, seven males, age 28.6 +/- 2.9 years, BMI 22.1 +/- 0.8 kg/m2). RESULTS: IGF-I levels in GHD were markedly lower than in NS (69.8 +/- 11.3 vs. 167.9 +/- 19.2 microg/l, P < 0.003). Ghrelin administration induced significant increase in GH, PRL, ACTH and cortisol levels in all GHD. In GHD, the GH response to ghrelin was higher (P < 0.05) than that to GHRH + ARG, which, in turn, was higher (P < 0.05) than that to ITT (9.2 +/- 4.1 vs. 5.3 +/- 1.7 vs. 1.4 +/- 0.4 microg/l). These GH (1 microg/l = 2 mU/l) responses in GHD were markedly lower (P < 0.0001) than those in NS (ghrelin vs. GHRH + ARG vs. ITT 92.1 +/- 16.7 vs. 65.3 +/- 8.9 vs. 17.7 +/- 3.5 microg/l). In GHD, the highest individual peak GH response to ghrelin was markedly lower than the lowest peak GH response in NS (28.5 vs. 42.9 microg/l). GHD and NS showed overlapping PRL (1 microg/l = 32 mU/l) (10.0 +/- 1.4 vs. 14.9 +/- 2.2 microg/l), ACTH (22.3 +/- 5.3 vs. 18.7 +/- 4.6 pmol/l) and cortisol responses (598.1 +/- 52.4 vs. 486.9 +/- 38.9 nmol/l). CONCLUSIONS: This study shows that ghrelin is one of the most powerful provocative stimuli of GH secretion, even in those patients with isolated severe GHD. In this condition, however, the somatotroph response is markedly reduced while the lactotroph and corticotroph responsiveness to ghrelin is fully preserved, indicating that this endocrine activity is fully independent of mechanisms underlying the GH-releasing effect. These results do not support the hypothesis that ghrelin deficiency is a major cause of isolated GH deficiency but suggest that ghrelin might represent a reliable provocative test to evaluate the maximal GH secretory capacity provided that appropriate cut-off limits are assumed.

Adrenocorticotropic Hormone↗

PubMed2002

Effects of glucose, free fatty acids or arginine load on the GH-releasing activity of ghrelin in humans.

OBJECTIVE: Ghrelin, a 28 amino acid peptide purified from the stomach and showing a unique structure with an n-octanoyl ester in serine-3 residue, is a natural ligand of the GH secretagogue (GHS) receptor (GHS-R) and strongly stimulates GH secretion. In humans, ghrelin is more potent than growth hormone-releasing hormone (GHRH) and non-natural GHS such as hexarelin. Moreover, ghrelin shows a true synergism with GHRH, has no interaction with hexarelin and, similarly to non-natural GHS, is partially refractory to the inhibitory effect of exogenous somatostatin (SS). Despite this evidence, the mechanisms underlying the GH-releasing effect of ghrelin in humans have not been fully clarified. SUBJECTS: To this aim we enrolled six normal young volunteers [age (mean +/- SEM) 28.9 +/- 3.1 year; body mass index 22.3 +/- 1.0 kg/m2). DESIGN AND MEASUREMENTS: In all subjects we studied the effects of glucose (OGTT, 100 g oral glucose at -45 min) or free fatty acids (FFA) load [lipid-heparin emulsion, Li-He, Intralipid 10% 250 ml + heparin 2500 U i.v. from -30 to +120 min] as well as of arginine (ARG, 0.5 g/kg infused from 0 to +30 min) on the GH response to human ghrelin (1.0 micro g/kg i.v. at 0 min) administration. These results were compared with those obtained by studying the effects of OGTT, Li-He and ARG on the GH response to GHRH-29 (1.0 micro g/kg i.v. at 0 min). RESULTS: The GH response to ghrelin (auc 5452.4 +/- 991.3 micro g/l/h) was higher (P < 0.05) than that after GHRH (1519.4 +/- 93.3 micro g/l/h). The GH response to GHRH was inhibited by OGTT (450.7 +/- 81.1 micro g/l/h, P < 0.05) and almost abolished by Li-He (230.0 +/- 63.6 micro g/l/h, P < 0.05) while was markedly potentiated by ARG (2520.4 +/- 425.8 micro g/l/h, P < 0.05). The GH response to GHRH + ARG, however, was lower (P < 0.05) than that to ghrelin alone. The GH response to ghrelin was blunted by OGTT (2153.1 +/- 781.9 micro g/l/h, P < 0.05) as well as by Li-He (3158.8 +/- 426.7 micro g/l/h, P < 0.05) but these responses remained higher (P < 0.05) than that to GHRH alone. On the other hand, ARG did not modify the GH response to ghrelin (6324.3 +/- 1275.5 micro g/l/h). For GH 1 micro g/l = 2 mU/l. CONCLUSIONS: In humans, ghrelin exerts a strong stimulatory effect on GH secretion which is partially refractory to the inhibitory effect of both glucose and FFA load and is not enhanced by ARG. These factors almost abolish and potentiate, respectively, the GH response to GHRH, at least partially, via modulation of hypothalamic SS release. Thus, our findings agree with the hypothesis that ghrelin as well as non-natural GHS acts, at least partially, by antagonizing SS activity.

Adult↗

PubMed2002

Ghrelin and synthetic GH secretagogues.

Ghrelin, a 28-amino-acid acylated peptide, produced mainly by the stomach, displays strong growth hormone-(GH)-releasing activity mediated by the hypothalamus-pituitary growth hormone potential secretagogue (GHS) receptor which had been shown to be specific for a family of synthetic, orally active GHS. GHS are reliable provocative tests for the diagnosis of GH deficiency but, as orally active growth-promoting agents, they are not comparable with human recombinant GH in terms of efficacy. The usefulness of GHS in anabolic, anti-ageing drug intervention in the somatopause is still unclear. GHS also act on central and peripheral receptors and show other actions, including an orexigenic effect, an influence on gastroentero-pancreatic functions, and cardiovascular and anti-proliferative effects. Ghrelin mediates the neuroendocrine and metabolic response to starvation. Taking into account its orexigenic effect, GHS analogues acting as agonists or antagonists on appetite could represent a new drug intervention for eating disorders.

Adrenocorticotropic Hormone↗

PubMed2002

Ghrelin secretion is inhibited by either somatostatin or cortistatin in humans.

Ghrelin possesses endocrine and non-endocrine actions mediated by the GH Secretagogue (GHS)-Receptors (GHS-R). The regulation of ghrelin secretion is still largely unknown. Somatostatin (SRIF) modulates central and gastroenteropancreatic hormonal secretions and functions. SRIF actions are partially shared by cortistatin (CST), a natural SRIF analogue, that binds all SRIF receptors and also GHS-R. Herein, we studied the effects of SRIF-14 or CST-14 (2.0 micro g/kg/h i.v. over 120 min) and of placebo on ghrelin, GH, insulin, glucagon and glucose levels in 6 normal young men. Placebo unaffected GH, insulin, glucagon, glucose and ghrelin levels. SRIF and CST similarly inhibited (p < 0.05) spontaneous GH secretion of about 90%. After SRIF or CST withdrawal, GH levels recovered to baseline levels. Both SRIF and CST similarly inhibited (p<0.01) insulin secretion of about 45%. In both sessions, after SRIF or CST withdrawal, insulin overrode baseline levels. Both SRIF and CST similarly inhibited (p < 0.01) glucagon levels of about 40%. After SRIF or CST withdrawal, glucagon persisted lower (p < 0.05) than at baseline. Neither SRIF nor CST modified glucose levels. Both SRIF and CST similarly inhibited (p < 0.01) circulating ghrelin levels of about 55%. Ghrelin levels progressively decreased from time +15 min, reaching the nadir at 120 and 105 min for SRIF and CST, respectively. Even 30 min after SRIF or CST withdrawal, ghrelin levels persisted lower (p < 0.05) than those at baseline. In conclusion, this study first shows that SRIF and CST strongly inhibits ghrelin secretion that, differently from GH and insulin secretion, persists inhibited even after stopping the infusion of SRIF or CST.

Adult↗

PubMed2002

Expression of ghrelin and of the GH secretagogue receptor by pancreatic islet cells and related endocrine tumors.

Ghrelin is a novel gastrointestinal hormone produced by rat and human gastric X-like neuroendocrine cells, which strongly stimulates GH secretion and influences energy balance, gastric motility, and acid secretion. Ghrelin is expressed in pituitary and gastrointestinal endocrine tumors. It binds to the GH secretagogue receptor (GHS-R), which is present in a wide variety of central and peripheral human tissues. The aim of the present study was 2-fold: 1) to determine, by immunohistochemistry and mRNA analysis, whether pancreatic islet cells produce ghrelin and express GHS-R; and 2) to investigate ghrelin and GHS-R expression in pancreatic endocrine tumors. Seven cases of nonneoplastic pancreatic tissue and 28 endocrine tumors were studied. In pancreatic islets, ghrelin immunoreactivity was present in all cases and confined to beta-cells. Eleven of the 28 (39%) endocrine tumors were immunoreactive for ghrelin. In situ hybridization and RT-PCR confirmed the immunohistochemical data for both tumors and islets but also revealed ghrelin mRNA in 8 and 11 additional tumors, respectively. GHS-R 1a and 1b mRNAs were present in 7 of 28 and 14 of 28 tumors, respectively, studied by RT-PCR. These findings demonstrate that ghrelin production is not restricted to the stomach but is also present in pancreatic beta-cells and endocrine tumors (regardless of the type of pancreatic hormone produced, if any). Expression of GHS-R in some of the endocrine tumors studied indicates that autocrine/paracrine circuits may be active in neoplastic conditions.

Adult↗

PubMed2002

Endocrine activities of cortistatin-14 and its interaction with GHRH and ghrelin in humans.

Cortistatin (CST)-14, a neuropeptide with high homology with somatostatin (SS)-14, binds all sst subtypes but, unlike SS, also ghrelin's receptor. In six normal adults, we studied the effects of CST-14 or SS-14 administration (2.0 micro g/kg/h iv) on: 1) GH and insulin secretion; 2) the GH response to GHRH (1.0 microg/kg i.v.); and 3) the GH, prolactin (PRL), ACTH, cortisol, insulin, and glucose responses to ghrelin (1.0 microg/kg i.v.). CST-14 inhibited GH and insulin secretion (P < 0.01) to the same extent of SS-14. The GH response to GHRH was similarly inhibited (P < 0.01) by either CST-14 or SS-14. Ghrelin released more GH than GHRH (P < 0.01); these responses were similarly inhibited (P < 0.05) by either CST-14 or SS-14, that made ghrelin-induced GH rise similar to that after GHRH alone. Neither CST-14 nor SS-14 modified PRL, ACTH, or cortisol responses to ghrelin. The inhibitory effect of CST-14 and SS-14 on insulin was unaffected by ghrelin that, in turn, reduced insulin secretion per se (P < 0.01). Ghrelin increased glucose levels (P < 0.05); CST-14 and SS-14 did not modify this effect. Thus, CST-14 inhibits both basal and stimulated GH secretion in humans to the same extent of SS-14. The GH-releasing activity of ghrelin seems partially resistant to CST-14 as well as SS-14. CST-14 and SS-14 do not affect PRL and ACTH secretion but, like ghrelin, inhibit insulin secretion; the ghrelin-induced inhibition is not additive with that of CST-14 or SS-14, suggesting a common mechanism of action on beta cell secretion.

Adrenocorticotropic Hormone↗

PubMed2002

Impact of two or three daily subcutaneous injections of hexarelin, a synthetic growth hormone (GH) secretagogue, on 24-h GH, prolactin, adrenocorticotropin and cortisol secretion in humans.

OBJECTIVE: To extend the insights on the action of GH secretagogues (GHS) on pituitary function, we studied the impact of intermittent daily s.c. administration of a peptidyl GHS, hexarelin (HEX), on 24-h GH, PRL, ACTH and cortisol release in healthy volunteers. DESIGN: We investigated the impact of two or three times daily s.c. administration of a short-acting peptidyl GHS, the hexapeptide HEX (1.5 microg/kg) on 24-h GH, PRL, ACTH and cortisol secretion (sampling every 20 min) in six normal young men. To monitor possible down-regulation, the effect of 1 microg/kg i.v. HEX at the end of each 24-h sampling period was studied. METHODS: Multi-parameter deconvolution analysis was used to quantitate pulsatile GH, PRL, ACTH and cortisol secretion and estimate the corresponding hormone half-lives. Complementary to deconvolution analysis, approximate entropy was used as a scale- and model-independent statistic to quantify the serial orderliness or pattern regularity of hormone measurements. RESULTS: Mean and integrated (24-h) serum GH concentrations were increased from baseline values to the same extent by two and three HEX injections. Both HEX schedules equally increased GH secretory burst mass (but not burst frequency), mean daily GH production rate, GH half-life and irregularity of GH release patterns. No change occurred in the secretion of IGF-I, PRL, ACTH and cortisol. Intravenous HEX at the end of each spontaneous 24-h profile induced a significant rise in GH, PRL, ACTH and cortisol. Prior HEX administration blunted the GH response, abolished that of ACTH and cortisol and did not modify the PRL increase. CONCLUSIONS: The study showed that two or three daily s.c. injections of HEX augmented 24-h GH secretion equally, amplifying selectively GH secretory pulse mass without altering lactotroph and corticotroph secretion. IGF-I levels were not modified by these 1-day HEX treatment schedules.

Adrenocorticotropic Hormone↗

PubMed2002

Central ghrelin production does not substantially contribute to systemic ghrelin concentrations: a study in two subjects with active acromegaly.

INTRODUCTION: In an animal model of acromegaly (PEPCK-hGH transgenic mice), low systemic levels of ghrelin have been observed compared with normal mice. We hypothesized that systemic circulating ghrelin levels are also decreased in humans with active acromegaly and that the contribution of central ghrelin production to systemic ghrelin levels is minimal. OBJECTIVES: The aim of the present study was to investigate, in two subjects with active acromegaly, whether there are differences between systemic ghrelin levels and ghrelin concentrations in the petrosal sinus. DESIGN: We measured systemic and central ghrelin levels in these two acromegalic patients by bilateral simultaneous inferior petrosal sinus sampling. Central and systemic blood samples were drawn before and 1, 5, 10, 15 and 20 min after stimulation with GH-releasing hormone (GHRH). Ghrelin was measured with a commercially available radioimmunoassay. RESULTS: In one acromegalic subject, the baseline systemic and central ghrelin levels were within the same range as in two non-acromegalic obese subjects. No gradient could be observed between central and systemic ghrelin concentrations. Stimulation with GHRH did not change the ghrelin concentrations in this patient. In the other acromegalic subject, the systemic ghrelin levels were also in the same range as in two non-acromegalic obese subjects. However, in this subject, baseline ghrelin concentrations in the right inferior petrosal vein were considerably lower than the systemic ghrelin concentrations, indicating a peripheral over central gradient. Administration of GHRH induced a significant rise in central ghrelin concentrations in the right inferior petrosal vein. Ghrelin levels in the left inferior petrosal vein and systemic ghrelin levels were in the normal range and GHRH stimulation did not change these concentrations. CONCLUSIONS: The absence of a central over peripheral ghrelin gradient in these two acromegalics indicated that circulating ghrelin is mainly produced peripherally. Circulating systemic ghrelin levels were not decreased in these two subjects with active acromegaly.

Acromegaly↗

PubMed2002

Ghrelin: much more than a natural growth hormone secretagogue.

Ghrelin, a 28 amino acid acylated peptide predominantly produced by the stomach, displays strong growth hormone-releasing activity mediated by the hypothalamus-pituitary GH secretagogue receptors that were found to be specific for a family of synthetic, orally active GH secretagogues. The discovery of ghrelin brings us to a new understanding of the regulation of GH secretion. However, ghrelin is much more than simply a natural GH secretagogue. It also acts on other central and peripheral receptors and exhibits other actions, including stimulation of lactotroph and corticotroph secretion, orexigenic, influences gastroenteropancreatic functions, and has metabolic, cardiovascular and antiproliferative effects. Knowledge of the whole spectrum of biologic activities of this new hormone will provide new understanding of some critical aspects of neuroscience, metabolism and internal medicine. In fact, GHS were born more than 20 years ago as synthetic molecules, eliciting the hope that orally active GHS could be used to treat GH deficiency as an alternative to recombinant human GH. However, the dream did not become reality and the usefulness of GHS as an anabolic anti-aging intervention restoring the GH/IGF-I axis in somatopause is still unclear. Instead, we now face the theoretic possibility that GHS analogues acting as agonists or antagonists could become candidate drugs for the treatment of pathophysiologic conditions in internal medicine totally unrelated to disorders of GH secretion.

Adrenocorticotropic Hormone↗

PubMed2002

Ghrelin: endocrine and non-endocrine actions.

Ghrelin, a 28-amino acid acylated peptide produced predominantly by the stomach, displays strong growth hormone (GH)-releasing activity via the hypothalamus-pituitary GH secretagogue (GHS) receptors that are specific for synthetic GHSs. Ghrelin's discovery changed our understanding of GH regulation. Evidence indicates that ghrelin also acts on other central and peripheral receptors and has other actions, including stimulation of lactotroph and corticotroph secretion; effects on gastroenteropancreatic functions; and orexigenic, metabolic, cardiovascular, and antiproliferative effects. When GHSs were developed more than 20 years ago as synthetic molecules, it was suggested that orally active GHSs might serve as alternatives to recombinant human GH for the treatment of GH deficiency. This proved not to be the case, however, and their utility as anabolic anti-aging agents to restore the GH-insulin-like growth factor-I axis during somatopause remains unclear. There is today, however, the possibility that GHS analogues could become candidate drugs for the treatment of conditions unrelated to disorders of GH secretion.

Animals↗