scholarly journals Ghrelin, Growth Hormone, and Insulin-like Growth Factor-I Levels in People With Protein C Deficiency

2021 ◽  
Author(s):  
Anna Dons-Jensen ◽  
Sascha Siig Horup ◽  
Anne-Mette Hvas ◽  
Esben Thyssen Vestergaard ◽  
Rakel Fuglsang Johansen
Keyword(s):  
Growth Hormone ◽  
Protein C ◽  
Endogenous Ligand ◽  
Protein C Deficiency ◽  
Gh Secretion ◽  
Index 2 ◽  
Acyl Ghrelin ◽  
Circulating Levels ◽  
Ghs Receptor

Abstract Acyl ghrelin (AG) is the endogenous ligand for the growth hormone (GH) secretagogue (GHS) receptor and exogenous AG is a strong stimulator of GH secretion [1]. The role of endogenous AG has not yet been unraveled and its regulation is complex, but it is widely accepted that circulating levels of ghrelin correlate inversely with body mass index [2]. The peptide known as unacylated ghrelin (UAG) is both a precursor to AG and one of the split products, when AG is deacylated during its degradation, so increased turnover of AG results in higher levels of UAG [3].

scholarly journals GH Does Not Modulate the Early Fasting-Induced Release of Free Fatty Acids in Mice

Endocrinology ◽  
2012 ◽  
Vol 153 (1) ◽  
pp. 273-282 ◽  
Author(s):  
F. J. Steyn ◽  
J. W. Leong ◽  
L. Huang ◽  
H. Y. Tan ◽  
T. Y. Xie ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Free Fatty Acids ◽  
Physiological Stress ◽  
Gh Secretion ◽  
Dynamic Relationship ◽  
Frequent Use ◽  
Initial Release ◽  
Acyl Ghrelin ◽  
Circulating Levels

Fasting results in the mobilization of adipose stores and the elevation of levels of free fatty acids (FFA). In humans, this process is driven by a release in GH. Little is known regarding the role of GH in modulating this process during early stages of fasting in the mouse. Confirmation of the role of GH in modulating FFA release in the fasting mouse is of particular importance given the frequent use of mouse models to study metabolic mechanisms. Here, we correlate the initial release of FFA throughout fasting in mice with pulsatile GH secretion. Observations illustrate the rapid release of FFA in response to food withdrawal. This does not correlate with a rise in GH secretion. Rather, we observed a striking loss in pulsatile secretion of GH throughout the first 6 h of fasting, suggesting that GH does not modulate the initial release of FFA in the mouse in response to fasting. This was confirmed in GH receptor knockout mice, in which we observed a robust fasting-induced rise in FFA. We further illustrate the dynamic relationship between the orexigenic and anorexigenic hormones ghrelin and leptin during fasting in the mouse. Our findings show an initial suppression of leptin and the eventual rise in circulating levels of acyl-ghrelin with fasting. However, altered acyl-ghrelin and leptin secretion occurs well after the rise in FFA and the suppression of GH secretion. Consequently, we conclude that although acyl-ghrelin and leptin may modulate the physiological response to drive food intake, these changes do not contribute to the initial loss of pulsatile GH secretion. Rather, it appears that the suppression of GH secretion in fasting may occur in response to an elevation in fasting levels of FFA or physiological stress. Observations highlight a divergent role for GH in modulating FFA release between man and mouse.

scholarly journals An Early Reduction in GH Peak Amplitude in Preproghrelin-Deficient Male Mice Has a Minor Impact on Linear Growth

Endocrinology ◽  
2014 ◽  
Vol 155 (9) ◽  
pp. 3561-3571 ◽  
Author(s):  
Rim Hassouna ◽  
Philippe Zizzari ◽  
Catherine Tomasetto ◽  
Johannes D. Veldhuis ◽  
Oriane Fiquet ◽  
...  
Keyword(s):  
Linear Growth ◽  
Pulse Amplitude ◽  
Endogenous Ligand ◽  
Gh Secretion ◽  
Gut Hormone ◽  
Igf I ◽  
Altered Response ◽  
Acyl Ghrelin ◽  
A Minor

Abstract Ghrelin is a gut hormone processed from the proghrelin peptide acting as the endogenous ligand of the GH secretagogue receptor 1a. The regulatory role of endogenous ghrelin on pulsatile GH secretion and linear growth had to be established. The aim of the present study was to delineate the endogenous actions of preproghrelin on peripheral and central components of the GH axis. Accordingly, the ultradian pattern of GH secretion was measured in young and old preproghrelin-deficient males. Blood samples were collected by tail bleeding every 10 minutes over a period of 6 hours. Analysis of the GH pulsatile pattern by deconvolution showed that GH was secreted in an ultradian manner in all genotypes, with major secretory peaks occurring at about 3-hour intervals. In older mice, the peak number was reduced and secretion was less irregular compared with younger animals. Remarkably, in young Ghrl−/− mice, the amplitude of GH secretory bursts was significantly reduced. In older mice, however, genotype differences were less significant. Changes in GH pulsatility in young Ghrl−/− mice were associated with a tendency for reduced GH pituitary contents and plasma IGF-I concentrations, but with only a minor impact on linear growth. In Ghrl+/− mice, despite reduced Acyl ghrelin to des-acyl ghrelin ratio, GH secretion was not impaired. Ghrelin deficiency was not associated with a reduction in hypothalamic GHRH content or altered response to GHRH stimulation. Therefore, reduction in GHRH production and/or sensitivity do not primarily account for the altered GH pulsatile secretion of young Ghrl−/− mice. Instead, GHRH expression was elevated in young but not old Ghrl−/− mice, suggesting that differential compensatory responses resulting from the absence of endogenous ghrelin is occurring according to age. These results show that endogenous ghrelin is a regulator of GH pulse amplitude in growing mice but does not significantly modulate linear growth.

scholarly journals Differential Diagnosis of the Short IGF-I-Deficient Child with Apparently Normal Growth Hormone Secretion

2021 ◽  
pp. 1-24
Author(s):  
Jan M. Wit ◽  
Sjoerd D. Joustra ◽  
Monique Losekoot ◽  
Hermine A. van Duyvenvoorde ◽  
Christiaan de Bruin
Keyword(s):  
Growth Hormone ◽  
Differential Diagnosis ◽  
Growth Hormone Secretion ◽  
Normal Growth ◽  
Stimulation Test ◽  
Healthy Children ◽  
Genetic Causes ◽  
Gh Secretion ◽  
Igf I

The current differential diagnosis for a short child with low insulin-like growth factor I (IGF-I) and a normal growth hormone (GH) peak in a GH stimulation test (GHST), after exclusion of acquired causes, includes the following disorders: (1) a decreased spontaneous GH secretion in contrast to a normal stimulated GH peak (“GH neurosecretory dysfunction,” GHND) and (2) genetic conditions with a normal GH sensitivity (e.g., pathogenic variants of <i>GH1</i> or <i>GHSR</i>) and (3) GH insensitivity (GHI). We present a critical appraisal of the concept of GHND and the role of 12- or 24-h GH profiles in the selection of children for GH treatment. The mean 24-h GH concentration in healthy children overlaps with that in those with GH deficiency, indicating that the previously proposed cutoff limit (3.0–3.2 μg/L) is too high. The main advantage of performing a GH profile is that it prevents about 20% of false-positive test results of the GHST, while it also detects a low spontaneous GH secretion in children who would be considered GH sufficient based on a stimulation test. However, due to a considerable burden for patients and the health budget, GH profiles are only used in few centres. Regarding genetic causes, there is good evidence of the existence of Kowarski syndrome (due to <i>GH1</i> variants) but less on the role of <i>GHSR</i> variants. Several genetic causes of (partial) GHI are known (<i>GHR</i>, <i>STAT5B</i>, <i>STAT3</i>, <i>IGF1</i>, <i>IGFALS</i> defects, and Noonan and 3M syndromes), some responding positively to GH therapy. In the final section, we speculate on hypothetical causes.

Effect of actively immunizing sheep against growth hormone-releasing hormone or somatostatin on spontaneous pulsatile and neostigmine-induced growth hormone secretion

1995 ◽  
Vol 144 (1) ◽  
pp. 83-90 ◽  
Author(s):  
E Magnan ◽  
L Mazzocchi ◽  
M Cataldi ◽  
V Guillaume ◽  
A Dutour ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Body Weight ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Physiological Role ◽  
Gh Secretion ◽  
Igf I ◽  
Plasma Gh ◽  
Hypophysial Portal

Abstract The physiological role of endogenous circulating GHreleasing hormone (GHRH) and somatostatin (SRIH) on spontaneous pulsatile and neostigmine-induced secretion of GH was investigated in adult rams actively immunized against each neuropeptide. All animals developed antibodies at concentrations sufficient for immunoneutralization of GHRH and SRIH levels in hypophysial portal blood. In the anti GHRH group, plasma GH levels were very low; the amplitude of GH pulses was strikingly reduced, although their number was unchanged. No stimulation of GH release was observed after neostigmine administration. The reduction of GH secretion was associated with a decreased body weight and a significant reduction in plasma IGF-I concentration. In the antiSRIH group, no changes in basal and pulsatile GH secretion or the GH response to neostigmine were observed as compared to controls. Body weight was not significantly altered and plasma IGF-I levels were reduced in these animals. These results suggest that in sheep, circulating SRIH (in the systemic and hypophysial portal vasculature) does not play a significant role in pulsatile and neostigmine-induced secretion of GH. The mechanisms of its influence on body weight and production of IGF-I remain to be determined. Journal of Endocrinology (1995) 144, 83–90

Paediatric thrombo-embolism: the influence of non-genetic factors and the role of activated protein C resistance and protein C deficiency

1997 ◽  
Vol 156 (4) ◽  
pp. 277-281 ◽  
Author(s):  
M. M. Uttenreuther-Fischer ◽  
B. Vetter ◽  
C. Hellmann ◽  
U. Otting ◽  
S. Ziemer ◽  
...  
Keyword(s):  
Protein C ◽  
Genetic Factors ◽  
Activated Protein C ◽  
Activated Protein C Resistance ◽  
Protein C Deficiency

Growth hormone and ageing

2011 ◽  
pp. 1483-1492
Author(s):  
James Gibney ◽  
Ken K. Y. Ho
Keyword(s):  
Growth Hormone ◽  
Body Composition ◽  
Bone Growth ◽  
Human Pituitary ◽  
Physiological Functions ◽  
Functional Changes ◽  
Gh Secretion ◽  
Period 2 ◽  
Age Related

Ageing is characterized by undesirable changes in body composition and a decline in many physiological functions, leading to reduced physical fitness and increased susceptibility to illness. With the projected growth of the elderly population worldwide, the ageing process is likely to give rise to increasing demands on health and welfare service budgets. The WHO projects that between the years 2000 and 2050, the world’s population of persons aged 60 and over will more than triple, from 600 million to 2 billion (1). The proportion of the EU population aged 65 years and over is predicted to rise from 17.1% in 2008 to 30.0% in 2060, and the proportion aged 80 and over to rise from 4.4% to 12.1% over the same period (2). Ageing is a complex and poorly understood process. In recent years, there has been considerable interest in the role of the growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis. Prior to 1985, supplies of GH were limited as it was obtainable only from human pituitary tissue, largely restricting its use to the treatment of childhood short stature. The development of recombinant GH has made available theoretically infinite supplies of GH, and allowed exploration of the role of GH in adult pathophysiology. While GH is best recognized for its stimulation of longitudinal bone growth in childhood, recent evidence has demonstrated that GH continues to play a central role in adulthood in the regulation of fat and protein metabolism, body composition, and many physiological functions. The steady decline in GH secretion through adulthood, termed the ‘somatopause,’ raises the possibility of involvement of the GH/IGF-1 axis in the structural and functional changes that accompany advancing age. This chapter explores the role of the somatopause and reviews the evidence for GH as a strategy for modifying age-related deterioration.

scholarly journals A Postweaning Reduction in Circulating Ghrelin Temporarily Alters Growth Hormone (GH) Responsiveness to GH-Releasing Hormone in Male Mice But Does Not Affect Somatic Growth

Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1743-1750 ◽  
Author(s):  
Hiroyuki Ariyasu ◽  
Hiroshi Iwakura ◽  
Go Yamada ◽  
Naotetsu Kanamoto ◽  
Mika Bando ◽  
...  
Keyword(s):  
Diphtheria Toxin ◽  
Somatic Growth ◽  
Male Mice ◽  
Wild Type ◽  
Endogenous Ligand ◽  
Gh Secretion ◽  
Igf I ◽  
Ghrelin Secretion ◽  
Physiologic Role

Ghrelin was initially identified as an endogenous ligand for the GH secretagogue receptor. When administrated exogenously, ghrelin stimulates GH release and food intake. Previous reports in ghrelin-null mice, which do not exhibit impaired growth nor appetite, question the physiologic role of ghrelin in the regulation of the GH/IGF-I axis. In this study, we generated a transgenic mouse that expresses human diphtheria toxin (DT) receptor (DTR) cDNA in ghrelin-secretion cells [ghrelin-promoter DTR-transgenic (GPDTR-Tg) mice]. Administration of DT to this mouse ablates ghrelin-secretion cells in a controlled manner. After injection of DT into GPDTR-Tg mice, ghrelin-secreting cells were ablated, and plasma levels of ghrelin were markedly decreased [nontransgenic littermates, 70.6 ± 10.2 fmol/ml vs. GPDTR-Tg, 5.3 ± 2.3 fmol/ml]. To elucidate the physiological roles of circulating ghrelin on GH secretion and somatic growth, 3-wk-old GPDTR-Tg mice were treated with DT twice a week for 5 wk. The GH responses to GHRH in male GPDTR-Tg mice were significantly lower than those in wild-type mice at 5 wk of age. However, those were normalized at 8 wk of age. In contrast, in female mice, there was no difference in GH response to GHRH between GPDTR-Tg mice and controls at 5 or 8 wk of age. The gender-dependent differences in response to GHRH were observed in ghrelin-ablated mice. However, GPDTR-Tg mice did not display any decreases in IGF-I levels or any growth retardation. Our results strongly suggest that circulating ghrelin does not play a crucial role in somatic growth.

Role of Growth Hormone (GH)-Releasing Hormone and Somatostatin on Leptin-Induced GH Secretion

1999 ◽  
Vol 69 (1) ◽  
pp. 3-10 ◽  
Author(s):  
E. Carro ◽  
R.M. Señarís ◽  
L.M. Seoane ◽  
L.A. Frohman ◽  
A. Arimura ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Releasing Hormone ◽  
Gh Secretion

scholarly journals Ghrelin Interacts with Human Plasma Lipoproteins

Endocrinology ◽  
2007 ◽  
Vol 148 (5) ◽  
pp. 2355-2362 ◽  
Author(s):  
Carine De Vriese ◽  
Mirjam Hacquebard ◽  
Françoise Gregoire ◽  
Yvon Carpentier ◽  
Christine Delporte
Keyword(s):  
Platelet Activating Factor ◽  
Peptide Hormone ◽  
Hydrolytic Activity ◽  
High Density ◽  
Plasma Lipoproteins ◽  
High Density Lipoproteins ◽  
Rat Serum ◽  
Gh Secretion ◽  
Acyl Ghrelin

Ghrelin, a peptide hormone produced predominantly by the stomach, stimulates food intake and GH secretion. The Ser3 residue of ghrelin is mainly modified by a n-octanoic acid. In the human bloodstream, ghrelin circulates in two forms: octanoylated and desacylated. We previously demonstrated that ghrelin is desoctanoylated in human serum by butyrylcholinesterase (EC 3.1.1.8) and other esterase(s), whereas in rat serum, only carboxylesterase (EC 3.1.1.1) is involved. The aims of this study were to determine the role of lipoprotein-associated enzymes in ghrelin desoctanoylation and the role of lipoproteins in the transport of circulating ghrelin. Our results show that ghrelin desoctanoylation mostly occurred in contact with low-density lipoproteins (LDLs) and lipoprotein-poor plasma subfractions. Butyrylcholinesterase and platelet-activating factor acetylhydrolase (EC 3.1.1.47) were responsible for the ghrelin hydrolytic activity of the lipoprotein-poor plasma and LDL subfractions, respectively. Moreover, we observed that ghrelin is associated with triglyceride-rich lipoproteins (TRLs), high-density lipoproteins (HDLs), very high-density lipoproteins (VHDLs), and to some extent LDLs. In conclusion, we report that the presence of the acyl group is necessary for ghrelin interaction with TRLs and LDLs but not HDLs and VHDLs. Ghrelin interacts via its N- and C-terminal parts with HDLs and VHDLs. This suggests that, whereas TRLs mostly transport acylated ghrelin, HDLs and VHDLs transport both ghrelin and des-acyl ghrelin.

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