Analysis of 24-hour plasma profiles of growth hormone (GH)-binding protein, GH/GH-binding protein-complex, and GH in healthy children.

Carlsson, Lena; Rosberg, Sten; Vitangcol, R. V.; Wong, Wai Lee; Albertsson‐Wikland, Kerstin

doi:10.1210/jcem.77.2.8345039

Cited by 26 publications

(10 citation statements)

References 15 publications

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“…In each individual, the relationship between leptin and the two other variables (insulin, cortisol) was determined by linear regression analysis. Profiles were subjected to pairwise cross-correlation analysis [23, 24, 25]. Cross-correlation analysis measures the degree of linear correlation between two sets of data at varying time lags (phase shifts).…”

Section: Methodsmentioning

confidence: 99%

Circadian Plasma Leptin Levels in Patients with Anorexia nervosa: Relation to Insulin and Cortisol

Herpertz¹,

Wagner²,

Albers

et al. 1998

Horm Res Paediatr

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In anorexia nervosa, underweight results from a loss of body mass due to a restricted energy intake. Circulating leptin levels have been shown to be low in the acute stage of the disorder. We studied diurnal secretion characteristics of leptin, insulin and cortisol in a study group of anorectic patients prior to refeeding, a second study group of anorectic patients after initiation of refeeding and study groups of healthy underweight and normal-weight controls. Spontaneous secretion of leptin, insulin and cortisol was measured by drawing blood samples every 2 h for 24 h. The temporal relationships between the diurnal secretion patterns of the three hormones were assessed by cross-correlation analysis in every study group. Plasma levels of leptin and cortisol were secreted with a specific circadian rhythmicity and displayed an intricate temporal relationship in anorectic patients. Semistarvation in the non-refed patients was associated with (1) exceedingly low plasma leptin levels, (2) a qualitative alteration in the circadian rhythm of leptin and cortisol levels and (3) an alteration in the temporal coupling between cortisol and leptin. In contrast, in the patients who had gained weight, leptin levels were higher; furthermore, the diurnal pattern of leptin and the temporal relationship between leptin and cortisol were similar to controls. Increments in insulin secretion preceded those of leptin by 4–6 h in both anorectic patients and in controls. Leptin levels increased 4 h prior to those of cortisol in controls and in refed patients, whereas in the non-refed patients cortisol increased prior to leptin. Thus, anorexia nervosa leads to pronounced, albeit reversible changes in the secretion dynamics of leptin and cortisol.

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Section: Methodsmentioning

confidence: 99%

Circadian Plasma Leptin Levels in Patients with Anorexia nervosa: Relation to Insulin and Cortisol

Herpertz¹,

Wagner²,

Albers

et al. 1998

Horm Res Paediatr

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“…As an initial approximation of the dynamics of GH secretion and removal in the absence and presence of a GH-BP, we assumed that a single high-affinity, lowcapacity, and specific GH-BP contributes predominantly to GH binding in plasma, i.e., that any contribution of other low-affinity BPs is relatively small by comparison, as has been shown (10,11,22). In addition, we provisionally assumed that (a) the turnover ofthe GH-BP is slow compared to that of free GH itself; (b) the intact GH-BP complex is removed at a rate that is slow compared to the clearance of free GH ( 18); (c) GH and BP mass are conserved; (d) the binding stoichiometry of GH to its BP is equimolar2; (e) the native elimination function for removal ofGH irreversibly from plasma is a single exponential, which acts only on free GH; (f) GH of 22,000-D molecular mass is measured and constitutes the principal circulating form of GH (23,24); (g) both bound and free GH are measured as immunoreactive GH (25); (h) GH is secreted in distinct pulses offinite half-duration (duration at half-maximal amplitude), amplitude, and mass; (i) BP concentration/activity is constant over time (26,27); and (j) the fate of a molecule ofGH injected into the bloodstream by the anterior pituitary gland includes entry into the free (protein unbound) compartment, possible association with the BP, dissociation from the BP, and/or irreversible elimination of free hormone by metabolic and excretory mechanisms.…”

Section: Methodsmentioning

confidence: 99%

Influence of the high-affinity growth hormone (GH)-binding protein on plasma profiles of free and bound GH and on the apparent half-life of GH. Modeling analysis and clinical applications.

Veldhuis¹,

Johnson²,

Faunt³

et al. 1993

J. Clin. Invest.

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The discovery of a specific high-affinity growth hormone (GH) binding protein (GH-BP) in plasma adds complexity to the dynamics of GH secretion and clearance. Intuitive predictions are that such a protein would damp sharp oscillations in GH concentrations otherwise caused by bursts ofGH secretion into the blood volume, prolong the apparent half-life of circulating GH, and contribute a reservoir function. To test these implicit considerations, we formulated an explicit mathematical model of pulsatile GH secretion and clearance in the presence or absence of a specific high-affinity GH-BP. Simulation experiments revealed that the pulsatile mode of physiological GH secretion creates a highly dynamic (nonequilibrium) system, in which the half-life of free GH, its instantaneous secretion rate, and the GH-BP affinity and capacity all contribute to defining momentary levels of free, bound, and total GH; the percentage of GH bound to protein; and the percentage occupancy of GH-BP. In contrast, the amount of free GH at equilibrium is specified only by the GH distribution volume and secretion rate and the half-life of free hormone. We conclude that the in vivo dynamics ofGH secretion, trapping, and clearance from the circulation offer a variety of regulatory loci at which the time structure of free, bound, and total GH delivery to target tissues can be controlled physiologically. (J. Clin. Invest. 1993. 91:629-641.)

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“…Serum GH was measured by the DSL-10-1900 active human GH ELISA kit (DSL, Webster, TX, USA), IGF-I-and IGF-binding protein 3 (IGFBP-3) measurements were performed using the IGF-I IRMA (radioisotopic assay kit; Nichols Institute Diagnostics, San Juan Capistrano, CA, USA) and the IGFBP-3 RIA kit (Nichols Institute Diagnostics) respectively. Serum GHBP was determined by a ligand-mediated immunofunctional assay (6).…”

Section: Subjectsmentioning

confidence: 99%

Primary GH insensitivity '(Laron syndrome) caused by a novel 4 kb deletion encompassing exon 5 of the GH receptor gene: effect of intermittent long-term treatment with recombinant human IGF-I

Besson

Salemi

Eblé

et al. 2004

European Journal of Endocrinology

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Objective: GH insensitivity syndrome (GHIS; Laron syndrome) is clinically characterized by severe postnatal growth failure and very low serum levels of IGF-I despite increased secretion of GH. This mainly autosomal recessive syndrome is clinically indistinguishable from isolated GH deficiency (IGHD). Fiftyone different mutations in the GH receptor (GHR) gene have been discovered, whereas only three deletions causing the disorder have been reported so far. In this report, we describe a consanguineous family from Sri Lanka with a novel deletion of 4097 bp in length encompassing exon 5. Subjects and methods: Parents of normal phenotype presented their second child (boy) to our clinic at the age of 7 months with severe growth retardation and the clinical features of IGHD (58 cm, 2 6.1 standard deviation score (SDS); 5.7 kg, 2 3.4 SDS). Assessment, however, revealed GHIS with absent GH-binding protein. Thereafter, the patient received intermittent recombinant human IGF-I (rhIGF-I; 80 mg/kg twice daily) treatment prepubertally for 5.5 years. Genomic DNA was extracted for genetic analysis and each exon was PCR amplified individually. Further, in order to amplify the GHR gene from exon 4 to 6, Expand Long Template PCR (Roche) was carried out. In addition, RNA isolation and RT-PCR were performed. Results: Separate PCRs of each of the exons of the GHR gene revealed that exon 5 in the patient was missing. Thereafter, 'Long PCR' from exons 4 to 6 revealed a 4097 bp deletion encompassing exon 5, in a homozygous state in the patient and in a heterozygous state in both parents. RT-PCR analysis revealed an exact absence of exon 5 resulting in a frameshift, leading to a stop codon in exon 6, which predicts a truncated, non-functional GHR protein. Conclusion: Fifty-one different mutations within the GHR gene causing GHIS have been reported so far. In contrast, only three deletions within the GHR gene are known. We describe a patient suffering from GHIS caused by a novel 4 kb deletion of the GHR gene encompassing exon 5 and, additionally, we focus on the effect of intermittent rhIGF-I treatment during prepuberty.European Journal of Endocrinology 150 635-642

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Analysis of 24-hour plasma profiles of growth hormone (GH)-binding protein, GH/GH-binding protein-complex, and GH in healthy children.

Cited by 26 publications

References 15 publications

Circadian Plasma Leptin Levels in Patients with Anorexia nervosa: Relation to Insulin and Cortisol

Circadian Plasma Leptin Levels in Patients with Anorexia nervosa: Relation to Insulin and Cortisol

Influence of the high-affinity growth hormone (GH)-binding protein on plasma profiles of free and bound GH and on the apparent half-life of GH. Modeling analysis and clinical applications.

Primary GH insensitivity '(Laron syndrome) caused by a novel 4 kb deletion encompassing exon 5 of the GH receptor gene: effect of intermittent long-term treatment with recombinant human IGF-I

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