Ghrelin: update on a novel hormonal system

Korbonits, Márta; Grossman, A.

doi:10.1530/eje.0.151s067

“…In obesity reduction in the half-life of GH (43) as well as a significant decrease in the production and secretion of the hormone have been reported (44). Among potential neuroendocrine causes of the marked impairment in spontaneous and stimulated GH secretion, GHRH hypoactivity has been shown but it is likely that alterations in the modulation of ghrelin, neuropeptide Y and/or leptin could have a role (45). Among metabolic factors, chronic elevation of non-esterified fatty acid levels and hyperinsulinism probably have a key role in reducing GH secretion in obesity (31,(46)(47)(48).…”

Section: Discussionmentioning

confidence: 99%

The cut-off limits of the GH response to GH-releasing hormone-arginine test related to body mass index

Corneli

¹

,

Somma

²

,

Baldelli

³

et al. 2005

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Objective: The diagnosis of growth hormone (GH) deficiency (GHD) in adults is based on a reduced peak GH response to provocative tests, such as the insulin tolerance test (ITT) and the GH-releasing hormone-arginine (GHRH-ARG) test. However, the cut-off limits of peak GH response in lean subjects are not reliable in obese patients; this is noteworthy since adult GHD is often associated with obesity. Aim of this study was to evaluate the diagnostic cut-off limits of peak GH response to the GHRH-ARG test in overweight and obese as well as in lean population. Design and methods: The GH responses to the GHRH-ARG test were studied in 322 patients with organic hypothalamic-pituitary disease and in 318 control subjects. Patients were subdivided into two groups on the basis of the number of pituitary hormone deficits, except for GH deficiency: (a) patients with total pituitary hormone deficit (TPHD) and (b) patients without or with no more than two pituitary hormone deficits (PHD). Both patients and control subjects were divided into three subgroups according to body mass index (BMI): lean (BMI , 25 kg/m 2 ), overweight (BMI $ 25 and , 30 kg/m 2 ) and obese (BMI $30 kg/m 2 ). TPHD patients were assumed to be GH deficient, whereas PHD patients may include subjects with either normal or impaired GH secretion. The statistical analysis was carried out by the Receiver-Operating Characteristic curve analysis (Medcalc 7.2). The diagnostic cut-off points were calculated for lean, overweight and obese subjects to provide optimal separation of GH-deficient patients and control subjects according to two criteria: (1) a balance between high sensitivity and high specificity; (2) to provide the highest pair of sensitivity/specificity values for GH deficiency. Results: In the lean population the best pair of values, with highest sensitivity as 98.7% and highest specificity as 83.7%, was found using a peak GH cut-off point of 11.5 mg/l. In the overweight population the best pair of values, 96.7 and 75.5%, respectively, was found using a peak GH cut-off point of 8.0 mg/l. In the obese population the best pair of values, 93.5 and 78.3%, respectively, was found using a peak GH cut-off point of 4.2 mg/l. Applying the above mentioned cut-off points, among PHD patients we found that 80 subjects (72%) were GHD whereas 31 (28%) had normal GH secretion. Conclusions: In conclusion the GHRH-ARG test is a reliable tool for the diagnosis of adult GH deficiency in lean, overweight and obese patients, provided that specific BMI-related cut-off limits are assumed.European Journal of Endocrinology 153 257-264

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“…1B). Since endogenous ghrelin expression is not detectable above background levels in cortex and is found only at very low levels in hypothalamus (16,17), it seems reasonable to conclude that the high levels of ghrelin mRNA in the L43 and L73 brains are overwhelmingly due to expression of the NSE-Ghr transgene. One key issue that is not addressed by these measurements is the degree to which the increased transgene results in increased levels of octanoylated ghrelin.…”

Section: Nse-ghr-positive Micementioning

confidence: 99%

“…GHRELIN IS A 28 AMINO-ACID PEPTIDE with a unique eight-carbon octanoyl group modification to the NH 2 -terminal third amino acid (17). Important roles for ghrelin include increasing food intake and body fat mass as well as stimulating growth hormone release and gastric motility (8,16,26).…”

mentioning

confidence: 99%

“…However, ghrelin is also expressed at lower levels in the small intestine and has been detected (17) at very low levels in many other tissues, including large intestine, pituitary, lung, placenta, ovary, testis, kidney, hypothalamus, and various endocrine tumors. The only known receptor for ghrelin is the growth hormone secretagogue receptor (GHS-R), which is expressed in several parts of the central nervous system [CNS; ventral tegmentum, substantia nigra, raphe nucleus, hippocampus, brainstem, and several hypothalamic nuclei, including the arcuate nucleus (ARC), paraventricular nucleus (PVN), ventromedial hypothalamic nucleus (VMN), anteroventral preoptic nucleus, anterior hypothalamic area, suprachiasmatic nucleus, anterolateral hypothalamic nucleus, and tuberomamillary nucleus (4,10,31)].…”

mentioning

confidence: 99%

“…Some studies (16,17) have shown that very low levels of ghrelin are expressed in the hypothalamus, but the significance of that expression remains unclear. Lall et al (18) used the rat growth hormone-releasing hormone promoter to drive expression of human GHS-R in mice.…”

mentioning

confidence: 99%

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Mice with chronically increased circulating ghrelin develop age-related glucose intolerance

Reed

¹

,

Benoit

²

,

Pfluger

³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

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Reed JA, Benoit SC, Pfluger PT, Tschö p MH, D'Alessio DA, Seeley RJ. Mice with chronically increased circulating ghrelin develop age-related glucose intolerance. Am J Physiol Endocrinol Metab 294: E752-E760, 2008. First published February 12, 2008 doi:10.1152/ajpendo.00463.2007.-Ghrelin is a gut peptide that stimulates food intake and increases body fat mass when administered centrally or peripherally. In this study, ghrelin was overexpressed in neurons using the neuron-specific enolase (NSE) promoter sequences and mouse ghrelin cDNA (NSE-Ghr). Ghrelin expression in NSE-Ghr brain tissues was increased compared with wild-type mice. Ghrelin expression was also increased to a much smaller extent in liver of these mice, but mRNA levels in stomach or duodenum did not differ from wild-type mice. Body weight and composition was analyzed in two lines of NSE-Ghr mice, one line with increased circulating bioactive ghrelin (L43) and one line without (L73). No increases in body weight, food intake, or fat mass were found. Energy expenditure was measured in L43 mice and did not differ from wild-type controls, whereas locomotor activity was increased in NSE-Ghr mice. Young NSE-Ghr mice had normal glucose tolerance; however, L43 NSE-Ghr mice, but not L73 mice, developed glucose intolerance at 32 wk of age. Despite the impaired glucose tolerance in L43 mice, insulin levels did not differ from those of wild-type mice. These findings suggest a role for ghrelin in age-associated impairments of glucose homeostasis. food intake; adipose; obesity GHRELIN IS A 28 AMINO-ACID PEPTIDE with a unique eight-carbon octanoyl group modification to the NH 2 -terminal third amino acid (17). Important roles for ghrelin include increasing food intake and body fat mass as well as stimulating growth hormone release and gastric motility (8,16,26). Other studies (2) have demonstrated a role for ghrelin in ACTH, cortisol, and prolactin release. Since the octanoyl modification appears to be required for all biological functions of ghrelin in vivo, the nonoctanoylated form, des-octanoyl ghrelin, has been thought (13) to be biologically inactive.Ghrelin was originally isolated from the stomach, and this tissue has the highest levels of ghrelin expression (16). However, ghrelin is also expressed at lower levels in the small intestine and has been detected (17) at very low levels in many other tissues, including large intestine, pituitary, lung, placenta, ovary, testis, kidney, hypothalamus, and various endocrine tumors. The only known receptor for ghrelin is the growth hormone secretagogue receptor (GHS-R), which is expressed in several parts of the central nervous system [CNS; ventral tegmentum, substantia nigra, raphe nucleus, hippocampus, brainstem, and several hypothalamic nuclei, including the arcuate nucleus (ARC), paraventricular nucleus (PVN), ventromedial hypothalamic nucleus (VMN), anteroventral preoptic nucleus, anterior hypothalamic area, suprachiasmatic nucleus, anterolateral hypothalamic nucleus, and tuberomamillary nucleus (4, 10, 31)]. Amo...

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Hormones, 2. Peptides and Proteins: Hypothalamic–Pituitary and Calcitropic Hormones

Sandow

¹

2013

Ullmann's Encyclopedia of Industrial Chemistry

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The article contains sections titled: 1. Introduction 2. Hypothalamic and Pituitary Hormones 2.1. The Hypothalamic–Pituitary System 2.2. Pituitary Hormone Preparations 2.2.1. Thyrotropin‐Releasing Hormone (TRH) 2.2.2. Thyrotropin (TSH) 2.2.3. Luteinizing Hormone Releasing Hormone (LHRH, GnRH) 2.2.4. Luteinizing Hormone (LH), Follitropin (FSH), Human Chorionic Gonadotropin (HCG) 2.3. Growth Hormone and Prolactin Regulation 2.3.1. Growth‐Hormone‐Releasing Hormone 2.3.2. Somatostatin 2.3.3. Growth Hormone 2.3.4. Prolactin and Human Placental Lactogen (HPL) 2.4. The Melanocortin System 2.4.1. Corticotropin‐Releasing Hormone (CRH) 2.4.2. Corticotropin (ACTH) 2.4.3. Melanocyte‐Stimulating Hormone (MSH) 2.4.4. Melanocortins 2.4.5. Proopiomelanocortin (POMC) Processing 2.5. New Hypothalamic–Pituitary Peptides 2.6. Neurohypophyseal Peptides 2.6.1. Vasopressin 2.6.2. Oxytocin 3. Calcium‐Regulating Hormones 3.1. Calcitonin 3.2. Parathormone

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Ghrelin: update on a novel hormonal system

Cited by 66 publications

References 23 publications

The cut-off limits of the GH response to GH-releasing hormone-arginine test related to body mass index

The cut-off limits of the GH response to GH-releasing hormone-arginine test related to body mass index

Mice with chronically increased circulating ghrelin develop age-related glucose intolerance

Hormones, 2. Peptides and Proteins: Hypothalamic–Pituitary and Calcitropic Hormones

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