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Amino Acids

, Volume 47, Issue 9, pp 1875–1883 | Cite as

Homoarginine (hArg) and asymmetric dimethylarginine (ADMA) in short stature children without and with growth hormone deficiency: hArg and ADMA are involved differently in growth in the childhood

  • Jennifer Langen
  • Arslan Arinc Kayacelebi
  • Bibiana Beckmann
  • Katharina Weigt-Usinger
  • Christina Carmann
  • Irina Hörster
  • Eggert Lilienthal
  • Annette Richter-Unruh
  • Dimitrios Tsikas
  • Thomas LückeEmail author
Original Article
Part of the following topical collections:
  1. Homoarginine, Arginine and Relatives

Abstract

Adult subjects with growth hormone (GH) deficiency (GHD) are known to have reduced life expectancy due to increased cardiovascular and cerebrovascular events. In adults, these events are associated with elevated circulating concentrations of asymmetric dimethylarginine (ADMA) which is an endogenous inhibitor of l-arginine (Arg)-derived nitric oxide (NO). Low circulating concentrations of homoarginine (hArg) emerged as a cardiovascular risk factor. In adults, hArg seems to antagonize ADMA. In the present work, we tested the hypothesis that children with short stature without or with GHD have altered Arg/NO pathway as compared to children with normal growth. We studied 66 short stature children (38 boys, 28 girls) aged 3.5–17.3 years, who underwent the routine l-Arginine Test to diagnose presence of GHD. GHD was confirmed in 47 children (GHD group; 30 boys, 17 girls) and was absent in the remaining 19 children (non-GHD group; 8 boys, 11 girls). In addition, we investigated 24 healthy age- and gender-matched children (10 boys, 14 girls) with normal growth. In EDTA plasma samples of all children, we determined by mass spectrometry-based methods the concentrations of Arg, hArg and ADMA, and calculated the Arg/ADMA and hArg/ADMA molar ratios. With respect to these biochemical parameters, we did not find statistically significant differences between the GHD and non-GHD groups. Comparing short with normal stature children, we found small differences regarding plasma hArg concentrations [mean ± SD; median (25th–75th percentile)]: 2.06 ± 0.52 µM; 2.12 (1.74–2.36) µM vs. 1.7 ± 0.5 µM; 1.6 (1.4–1.8) µM, P < 0.001. Compared to normal stature children, short stature children had considerably higher plasma concentrations of ADMA [0.77 ± 0.15 µM; 0.77 (0.66–0.85) µM vs. 0.57 ± 0.09 µM; 0.58 (0.50–0.63) µM, P < 0.001], but not of Arg [83.3 ± 19.2 µM; 82.2 (71.9–90.3) µM vs. 86.5 ± 17.8 µM; 84.8 (77.2–94.8) µM, P = 0.336], or the hArg/ADMA ratio [2.74 ± 0.76; 2.7 (2.2–3.1) vs. 3.1 ± 1.2; 2.85 (2.42–3.66), P = 0.161. hArg in the GHD group (r = 0.41, P = 0.004) and the hArg/ADMA ratio in both groups (r = 0.44, P = 0.002 in GHD; r = 0.55, P = 0.01 in non-GHD)], but not ADMA were positively correlated with insulin-like growth factor-1 (IGF-1). hArg and hArg/ADMA differed between girls and boys in the GHD and non-GHD groups but in the normal growth group. The hArg/ADMA ratio increased with age in all groups. Our study suggests that hArg and ADMA are involved in growth in the childhood, presumably in an antagonistic manner, with ADMA slowing and hArg accelerating growth.

Keywords

ADMA Arginine Children Growth hormone Homoarginine IGF-1 Short stature 

Abbreviations

ADMA

Asymmetric dimethylarginine

AGAT

Arginine:glycine amidinotransferase

Arg

l-Arginine

BMI

Body mass index

GH

Growth hormone

GHD

Growth hormone deficiency

hArg

l-Homoarginine

IGF-1

Insulin-like growth factor 1

IGFBP

Insulin-like growth factor binding protein

NO

Nitric oxide

NOS

Nitric oxide synthase

PTH

Parathyroid hormone

QC

Quality control

TSH

Thyroid stimulating hormone

Notes

Conflict of interest

The authors declare that they have no conflict of interest.

Compliance with ethical standards

Accepted principles of ethical and professional conduct have been followed. The studies were approved by the Ethics Committees of the Bochum University. Informed consent of the parents of the children involved in the study was obtained.

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Copyright information

© Springer-Verlag Wien 2015

Authors and Affiliations

  • Jennifer Langen
    • 1
  • Arslan Arinc Kayacelebi
    • 2
  • Bibiana Beckmann
    • 2
  • Katharina Weigt-Usinger
    • 1
  • Christina Carmann
    • 1
  • Irina Hörster
    • 1
  • Eggert Lilienthal
    • 3
  • Annette Richter-Unruh
    • 4
  • Dimitrios Tsikas
    • 2
  • Thomas Lücke
    • 1
    Email author
  1. 1.Department of Neuropaediatrics, Children’s HospitalUniversity of BochumBochumGermany
  2. 2.Centre of Pharmacology and ToxicologyHannover Medical SchoolHannoverGermany
  3. 3.Section of Endocrinology, Children’s HospitalUniversity of BochumBochumGermany
  4. 4.Department of Endocrinology, Children’s HospitalUniversity of MünsterMünsterGermany

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