GHRH plus arginine and arginine administration evokes the same ratio of GH isoforms levels in young patients with Prader-Willi syndrome

Antonello E Rigamonti, Antonino Crinò, Sarah Bocchini, Alessio Convertino, Martin Bidlingmaier, Michael Haenelt, Sofia Tamini, Silvano G Cella, Graziano Grugni, Alessandro Sartorio

Research output: Contribution to journalArticle

Abstract

Human GH is present in pituitary and circulation as several isoforms, the prevalent being 22kDa- and 20kDa-GH. Recently, we have demonstrated the preservation of a normal balance in GH isoforms after GH releasing hormone (GHRH) plus arginine (ARG) administration in adult patients with Prader-Willi syndrome (PWS), one of the most common causes of syndromic obesity, often associated with GH deficiency (GHD). Aim of the present study was to measure circulating levels of 22kDa- and 20kDa-GH in young PWS patients (n=24; F/M: 10/14; genotype UPD/DEL/met+: 11/11/2; age: 10.8±5.3years; BMI SDS: 2.0±2.0; GHD: 16/24; obesity: 12/24) after combined GHRH+ARG or ARG administration. The results were analysed subdividing the GHRH+ARG and ARG groups on the basis of PWS genotype, GHD status and obesity. Circulating levels of 22kDa- and 20kDa-GH were measured by a chemiluminescent or fluorescent method based on specific pairs of monoclonal antibodies. GHRH+ARG or ARG significantly stimulated the secretion of 22kDa-GH but not that of 20kDa-GH in all PWS patients. No significant GHRH+ARG- vs. ARG-induced changes in the ratios of 22kDa- to 20kDa-GH peaks were observed in all PWS patients, although 22kDa- or 20kDa-GH peaks were significantly higher in the GHRH+ARG than ARG group. When subdividing PWS patients in UPD vs. DEL, obese vs. non obese and GHD vs. non GHD subgroups, GH peaks were significantly higher in nonobese than obese patients and in non GHD than GHD patients administered with either GHRH+ARG or ARG test, apart from the comparisons in the DEL/UPD subgroups. Anyway, the ratios of peak levels of 22kDa- to 20kDa-GH were similar after GHRH+ARG vs. ARG in all subgroups investigated. In conclusion, this study shows that administration of two different pharmacological tests, i.e. ARG, capable of reducing hypothalamic somatostatinergic tone, and GHRH (+ARG), that directly acts at pituitary level on the somatotropic cell, evokes the same ratios of GH isoforms in young PWS patients, suggesting that the hypothalamic dysfunction in this genetic disorder does not alter the qualitative and quantitative composition of GH isoforms present in circulation.

Original languageEnglish
Pages (from-to)13-18
Number of pages6
JournalGrowth Hormone and IGF Research
Volume39
DOIs
Publication statusPublished - Apr 2018

Fingerprint

Prader-Willi Syndrome
Arginine
Protein Isoforms
Hormones
Obesity
Genotype
Inborn Genetic Diseases

Keywords

  • Adolescent
  • Arginine/administration & dosage
  • Biomarkers/blood
  • Child
  • Child, Preschool
  • Drug Therapy, Combination
  • Female
  • Growth Hormone-Releasing Hormone/administration & dosage
  • Hormones/administration & dosage
  • Human Growth Hormone/blood
  • Humans
  • Insulin-Like Growth Factor I/analysis
  • Male
  • Prader-Willi Syndrome/blood
  • Prognosis
  • Protein Isoforms

Cite this

GHRH plus arginine and arginine administration evokes the same ratio of GH isoforms levels in young patients with Prader-Willi syndrome. / Rigamonti, Antonello E; Crinò, Antonino; Bocchini, Sarah; Convertino, Alessio; Bidlingmaier, Martin; Haenelt, Michael; Tamini, Sofia; Cella, Silvano G; Grugni, Graziano; Sartorio, Alessandro.

In: Growth Hormone and IGF Research, Vol. 39, 04.2018, p. 13-18.

Research output: Contribution to journalArticle

@article{d459e602deb349e29605c67617ecc5af,
title = "GHRH plus arginine and arginine administration evokes the same ratio of GH isoforms levels in young patients with Prader-Willi syndrome",
abstract = "Human GH is present in pituitary and circulation as several isoforms, the prevalent being 22kDa- and 20kDa-GH. Recently, we have demonstrated the preservation of a normal balance in GH isoforms after GH releasing hormone (GHRH) plus arginine (ARG) administration in adult patients with Prader-Willi syndrome (PWS), one of the most common causes of syndromic obesity, often associated with GH deficiency (GHD). Aim of the present study was to measure circulating levels of 22kDa- and 20kDa-GH in young PWS patients (n=24; F/M: 10/14; genotype UPD/DEL/met+: 11/11/2; age: 10.8±5.3years; BMI SDS: 2.0±2.0; GHD: 16/24; obesity: 12/24) after combined GHRH+ARG or ARG administration. The results were analysed subdividing the GHRH+ARG and ARG groups on the basis of PWS genotype, GHD status and obesity. Circulating levels of 22kDa- and 20kDa-GH were measured by a chemiluminescent or fluorescent method based on specific pairs of monoclonal antibodies. GHRH+ARG or ARG significantly stimulated the secretion of 22kDa-GH but not that of 20kDa-GH in all PWS patients. No significant GHRH+ARG- vs. ARG-induced changes in the ratios of 22kDa- to 20kDa-GH peaks were observed in all PWS patients, although 22kDa- or 20kDa-GH peaks were significantly higher in the GHRH+ARG than ARG group. When subdividing PWS patients in UPD vs. DEL, obese vs. non obese and GHD vs. non GHD subgroups, GH peaks were significantly higher in nonobese than obese patients and in non GHD than GHD patients administered with either GHRH+ARG or ARG test, apart from the comparisons in the DEL/UPD subgroups. Anyway, the ratios of peak levels of 22kDa- to 20kDa-GH were similar after GHRH+ARG vs. ARG in all subgroups investigated. In conclusion, this study shows that administration of two different pharmacological tests, i.e. ARG, capable of reducing hypothalamic somatostatinergic tone, and GHRH (+ARG), that directly acts at pituitary level on the somatotropic cell, evokes the same ratios of GH isoforms in young PWS patients, suggesting that the hypothalamic dysfunction in this genetic disorder does not alter the qualitative and quantitative composition of GH isoforms present in circulation.",
keywords = "Adolescent, Arginine/administration & dosage, Biomarkers/blood, Child, Child, Preschool, Drug Therapy, Combination, Female, Growth Hormone-Releasing Hormone/administration & dosage, Hormones/administration & dosage, Human Growth Hormone/blood, Humans, Insulin-Like Growth Factor I/analysis, Male, Prader-Willi Syndrome/blood, Prognosis, Protein Isoforms",
author = "Rigamonti, {Antonello E} and Antonino Crin{\`o} and Sarah Bocchini and Alessio Convertino and Martin Bidlingmaier and Michael Haenelt and Sofia Tamini and Cella, {Silvano G} and Graziano Grugni and Alessandro Sartorio",
note = "Copyright {\circledC} 2017 Elsevier Ltd. All rights reserved.",
year = "2018",
month = "4",
doi = "10.1016/j.ghir.2017.11.005",
language = "English",
volume = "39",
pages = "13--18",
journal = "Endocrinology and Metabolism, Supplement",
issn = "1096-6374",
publisher = "Churchill Livingstone",

}

TY - JOUR

T1 - GHRH plus arginine and arginine administration evokes the same ratio of GH isoforms levels in young patients with Prader-Willi syndrome

AU - Rigamonti, Antonello E

AU - Crinò, Antonino

AU - Bocchini, Sarah

AU - Convertino, Alessio

AU - Bidlingmaier, Martin

AU - Haenelt, Michael

AU - Tamini, Sofia

AU - Cella, Silvano G

AU - Grugni, Graziano

AU - Sartorio, Alessandro

N1 - Copyright © 2017 Elsevier Ltd. All rights reserved.

PY - 2018/4

Y1 - 2018/4

N2 - Human GH is present in pituitary and circulation as several isoforms, the prevalent being 22kDa- and 20kDa-GH. Recently, we have demonstrated the preservation of a normal balance in GH isoforms after GH releasing hormone (GHRH) plus arginine (ARG) administration in adult patients with Prader-Willi syndrome (PWS), one of the most common causes of syndromic obesity, often associated with GH deficiency (GHD). Aim of the present study was to measure circulating levels of 22kDa- and 20kDa-GH in young PWS patients (n=24; F/M: 10/14; genotype UPD/DEL/met+: 11/11/2; age: 10.8±5.3years; BMI SDS: 2.0±2.0; GHD: 16/24; obesity: 12/24) after combined GHRH+ARG or ARG administration. The results were analysed subdividing the GHRH+ARG and ARG groups on the basis of PWS genotype, GHD status and obesity. Circulating levels of 22kDa- and 20kDa-GH were measured by a chemiluminescent or fluorescent method based on specific pairs of monoclonal antibodies. GHRH+ARG or ARG significantly stimulated the secretion of 22kDa-GH but not that of 20kDa-GH in all PWS patients. No significant GHRH+ARG- vs. ARG-induced changes in the ratios of 22kDa- to 20kDa-GH peaks were observed in all PWS patients, although 22kDa- or 20kDa-GH peaks were significantly higher in the GHRH+ARG than ARG group. When subdividing PWS patients in UPD vs. DEL, obese vs. non obese and GHD vs. non GHD subgroups, GH peaks were significantly higher in nonobese than obese patients and in non GHD than GHD patients administered with either GHRH+ARG or ARG test, apart from the comparisons in the DEL/UPD subgroups. Anyway, the ratios of peak levels of 22kDa- to 20kDa-GH were similar after GHRH+ARG vs. ARG in all subgroups investigated. In conclusion, this study shows that administration of two different pharmacological tests, i.e. ARG, capable of reducing hypothalamic somatostatinergic tone, and GHRH (+ARG), that directly acts at pituitary level on the somatotropic cell, evokes the same ratios of GH isoforms in young PWS patients, suggesting that the hypothalamic dysfunction in this genetic disorder does not alter the qualitative and quantitative composition of GH isoforms present in circulation.

AB - Human GH is present in pituitary and circulation as several isoforms, the prevalent being 22kDa- and 20kDa-GH. Recently, we have demonstrated the preservation of a normal balance in GH isoforms after GH releasing hormone (GHRH) plus arginine (ARG) administration in adult patients with Prader-Willi syndrome (PWS), one of the most common causes of syndromic obesity, often associated with GH deficiency (GHD). Aim of the present study was to measure circulating levels of 22kDa- and 20kDa-GH in young PWS patients (n=24; F/M: 10/14; genotype UPD/DEL/met+: 11/11/2; age: 10.8±5.3years; BMI SDS: 2.0±2.0; GHD: 16/24; obesity: 12/24) after combined GHRH+ARG or ARG administration. The results were analysed subdividing the GHRH+ARG and ARG groups on the basis of PWS genotype, GHD status and obesity. Circulating levels of 22kDa- and 20kDa-GH were measured by a chemiluminescent or fluorescent method based on specific pairs of monoclonal antibodies. GHRH+ARG or ARG significantly stimulated the secretion of 22kDa-GH but not that of 20kDa-GH in all PWS patients. No significant GHRH+ARG- vs. ARG-induced changes in the ratios of 22kDa- to 20kDa-GH peaks were observed in all PWS patients, although 22kDa- or 20kDa-GH peaks were significantly higher in the GHRH+ARG than ARG group. When subdividing PWS patients in UPD vs. DEL, obese vs. non obese and GHD vs. non GHD subgroups, GH peaks were significantly higher in nonobese than obese patients and in non GHD than GHD patients administered with either GHRH+ARG or ARG test, apart from the comparisons in the DEL/UPD subgroups. Anyway, the ratios of peak levels of 22kDa- to 20kDa-GH were similar after GHRH+ARG vs. ARG in all subgroups investigated. In conclusion, this study shows that administration of two different pharmacological tests, i.e. ARG, capable of reducing hypothalamic somatostatinergic tone, and GHRH (+ARG), that directly acts at pituitary level on the somatotropic cell, evokes the same ratios of GH isoforms in young PWS patients, suggesting that the hypothalamic dysfunction in this genetic disorder does not alter the qualitative and quantitative composition of GH isoforms present in circulation.

KW - Adolescent

KW - Arginine/administration & dosage

KW - Biomarkers/blood

KW - Child

KW - Child, Preschool

KW - Drug Therapy, Combination

KW - Female

KW - Growth Hormone-Releasing Hormone/administration & dosage

KW - Hormones/administration & dosage

KW - Human Growth Hormone/blood

KW - Humans

KW - Insulin-Like Growth Factor I/analysis

KW - Male

KW - Prader-Willi Syndrome/blood

KW - Prognosis

KW - Protein Isoforms

U2 - 10.1016/j.ghir.2017.11.005

DO - 10.1016/j.ghir.2017.11.005

M3 - Article

C2 - 29217318

VL - 39

SP - 13

EP - 18

JO - Endocrinology and Metabolism, Supplement

JF - Endocrinology and Metabolism, Supplement

SN - 1096-6374

ER -