The Role of Growth Hormone Receptor Isoforms and Their Effects in Bone Metabolism and Skeletal Fragility

2020 ◽  
Vol 27 (12) ◽  
pp. 1260-1267
Author(s):  
Sabrina Chiloiro ◽  
Federica Mirra ◽  
Donfrancesco Federico ◽  
Antonella Giampietro ◽  
Felicia Visconti ◽  
...  

Acromegaly and Growth Hormone Deficiency (GHD) are associated with skeletal fragility and with an increased prevalence of Vertebral Fractures (VFs). In the most recent years, several authors tried to investigate surrogate markers that may predict the risk of bone fragility in these endocrine disorders. The aim of this review is to evaluate the role of GH receptor polymorphisms in skeletal fragility in patients affected by GHD and acromegaly. In fact, until now, two different isoforms of the GH Receptor (GHR) were described, that differ for the presence or the absence of transcription of the exon 3 of the GHR gene. Both the isoforms produce a functioning receptor, but the exon 3-deleted isoforms (d3-GHR) has a higher sensitivity to endogenous and recombinant GH as compared to the full-length isoform (fl-GHR).

2019 ◽  
Vol 20 (7) ◽  
pp. 1608 ◽  
Author(s):  
Bowen Hu ◽  
Shuang Hu ◽  
Minmin Yang ◽  
Zhiying Liao ◽  
Dexiang Zhang ◽  
...  

The growth hormone receptor (GHR) gene is correlated with many phenotypic and physiological alternations in chicken, such as shorter shanks, lower body weight and muscle mass loss. However, the role of the GHR gene in mitochondrial function remains unknown in poultry. In this study, we assessed the function of mitochondria in sex-linked dwarf (SLD) chicken skeletal muscle and interfered with the expression of GHR in DF-1 cells to investigate the role of the GHR gene in chicken mitochondrial function both in vivo and in vitro. We found that the expression of key regulators of mitochondrial biogenesis and mitochondrial DNA (mtDNA)-encoded oxidative phosphorylation (OXPHOS) genes were downregulated and accompanied by reduced enzymatic activity of OXPHOS complexes in SLD chicken skeletal muscle and GHR knockdown cells. Then, we assessed mitochondrial function by measuring mitochondrial membrane potential (ΔΨm), mitochondrial swelling, reactive oxygen species (ROS) production, malondialdehyde (MDA) levels, ATP levels and the mitochondrial respiratory control ratio (RCR), and found that mitochondrial function was impaired in SLD chicken skeletal muscle and GHR knockdown cells. In addition, we also studied the morphology and structure of mitochondria in GHR knockdown cells by transmission electron microscopy (TEM) and MitoTracker staining. We found that knockdown of GHR could reduce mitochondrial number and alter mitochondrial structure in DF-1 cells. Above all, we demonstrated for the first time that the GHR gene is essential for chicken mitochondrial function in vivo and in vitro.


1992 ◽  
Vol 126 (2) ◽  
pp. 155-161 ◽  
Author(s):  
Geoffrey R Ambler ◽  
Bernhard H Breier ◽  
Andrzej Surus ◽  
Hugh T Blair ◽  
Stuart N McCutcheon ◽  
...  

We evaluated the interrelationship between, and regulation of, the hepatic growth hormone receptor and serum GH binding protein (GH BP) in pigs treated with recombinant porcine growth hormone (rpGH). Infant and pubertal male pigs (N = 5 per group) received either rpGH 0.15 mg/kg daily or diluent intramuscularly for 12 days. Somatic growth, serum IGF-I and GH BP and [125I]bovine GH (bGH) binding to MgCl2-treated hepatic membrane homogenates were examined. Marked age-related increases were seen in serum GH BP (p<0.001) and [125I]bGH binding to hepatic membranes (p<0.001). GH BP was increased in rpGH treated animals (p = 0.03), from 13.8±1.2 (mean±1 x sem) (controls) to 17.8±2.0% in infants, and from 35.2±2.6 (controls) to 41.8±3.4% in pubertal animals. [125I]bGH binding to hepatic membranes was also increased by rpGH treatment (p<0.05), from 7.0±1.6 (controls) to 15.4±3.6% in infants and from 53.7±7.1 (controls) to 65.1±11.8% in pubertal animals. No significant interaction between age and treatment was seen. Overall, serum GH BP correlated significantly with [125I]bGH membrane capacity (r=0.82, p<0.001), with a correlation of r= 0.83 in the infant animals but no significant correlation in the pubertal animals considered alone (r=0.13). Serum IGF-I correlated significantly with serum GH BP (r=0.93, p<0.001) and [125]bGH membrane binding capacity (r = 0.91, p< 0.001). These observations suggest that serum GH BP levels reflect major changes of hepatic GH receptor status. In addition, the present study demonstrates that the hepatic GH receptor can be induced by GH in the infant pig, despite a developmentally low GH receptor population at this age, suggesting potential efficacy of GH at earlier ages than generally considered.


2018 ◽  
Vol 39 ◽  
pp. 29-33 ◽  
Author(s):  
Merlin G. Butler ◽  
Waheeda Hossain ◽  
Maaz Hassan ◽  
Ann M. Manzardo

Author(s):  
Guy Van Vliet

Between embryonic life and the end of growth, the endocrine milieu undergoes profound changes that need to be known to understand the common paediatric endocrine disorders, to interpret results of hormone assays in newborns, infants, children, and adolescents properly, and to take advantage of some periods of life that are ‘windows of opportunity’ for some diagnoses. In this section, we will review these changes from the perspective of a practising paediatric endocrinologist. The main focus is on the ‘classical’ endocrine axes—growth hormone-releasing hormone (GHRH)/somatostatin–growth hormone–insulin-like growth factor, gonadotropin-releasing hormone–luteinizing hormone/follicle-stimulating hormone (FSH)–gonadal hormones, TRH–TSH–thyroid hormones, corticotropin-releasing factor–-adrenocorticotropin (ACTH)–adrenal steroids. Glucose and mineral metabolism will also be briefly discussed, as will childhood obesity. The increasing role of DNA-based diagnosis in paediatric endocrinology will also be highlighted.


2019 ◽  
Vol 31 (4) ◽  
pp. e12692 ◽  
Author(s):  
Antonio Bianchi ◽  
Antonella Giampietro ◽  
Linda Tartaglione ◽  
Sabrina Chiloiro ◽  
Raffaella Gentilella ◽  
...  

Genetics ◽  
2006 ◽  
Vol 173 (4) ◽  
pp. 2151-2164 ◽  
Author(s):  
Sirja Viitala ◽  
Joanna Szyda ◽  
Sarah Blott ◽  
Nina Schulman ◽  
Martin Lidauer ◽  
...  

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