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The consequences of growth hormone‐releasing hormone receptor haploinsufficiency for bone quality and insulin resistance
Author(s) -
Gois Miburge B.,
Salvatori Roberto,
AguiarOliveira Manuel H.,
Pereira Francisco A.,
Oliveira Carla R. P.,
OliveiraNeto Luiz A.,
C. Pereira Rossana M.,
Souza Anita H. O.,
Melo Enaldo V.,
de Paula Francisco J. A.
Publication year - 2012
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2011.04263.x
Subject(s) - haploinsufficiency , medicine , endocrinology , insulin resistance , hormone , growth hormone , hormone receptor , receptor , insulin , biology , phenotype , gene , genetics , cancer , breast cancer
Summary Objective Growth hormone (GH)/insulin‐like growth factor (IGF) axis and insulin are key determinants of bone remodelling. Homozygous mutations in the GH‐releasing hormone receptor (GHRHR) gene ( GHRHR ) are a frequent cause of genetic isolated GH deficiency (IGHD). Heterozygosity for GHRHR mutation causes changes in body composition and possibly an increase in insulin sensitivity, but its effects on bone quality are still unknown. The objective of this study was to assess the bone quality and metabolism and its correlation with insulin sensitivity in subjects heterozygous for a null mutation in the GHRHR . Patients and methods A cross‐sectional study was performed on 76 normal subjects (68·4% females) (N/N) and 64 individuals (64·1% females) heterozygous for a mutation in the GHRHR (MUT/N). Anthropometric features, quantitative ultrasound (QUS) of the heel, bone markers [osteocalcin (OC) and CrossLaps], IGF‐I, glucose and insulin were measured, and homeostasis model assessment of insulin resistance (HOMA IR ) was calculated. Results There were no differences in age or height between the two groups, but weight ( P = 0·007) and BMI ( P = 0·001) were lower in MUT/N. There were no differences in serum levels of IGF‐I, glucose, T‐ score or absolute values of stiffness and OC, but insulin ( P = 0·01), HOMA IR ( P = 0·01) and CrossLaps ( P = 0·01) were lower in MUT/N. There was no correlation between OC and glucose, OC and HOMA IR in the 140 individuals as a whole or in the separate MUT/N or N/N groups. Conclusions This study suggests that one allele mutation in the GHRHR gene has a greater impact on energy metabolism than on bone quality.