Impact of Growth Hormone (GH) Deficiency and GH Replacement upon Thymus Function in Adult Patients

Gabriel Morrhaye,Henri J Martens,Yves Beguin,Michel Moutschen,Jean-Jacques Legros,Frederic Baron,Remi Cheynier,Vincent Geenen,Hamid Kermani,Derya Unutmaz

doi:10.1371/journal.pone.0005668

Gabriel Morrhaye, Henri J Martens + Show 8 more

Open Access

https://doi.org/10.1371/journal.pone.0005668

Copy DOI

Journal: PloS one	Publication Date: May 22, 2009
Citations: 84	License type: CC BY 4.0

Affiliation: University of Liège, Institut Pasteur

Abstract

BackgroundDespite age-related adipose involution, T cell generation in the thymus (thymopoiesis) is maintained beyond puberty in adults. In rodents, growth hormone (GH), insulin-like growth factor-1 (IGF-1), and GH secretagogues reverse age-related changes in thymus cytoarchitecture and increase thymopoiesis. GH administration also enhances thymic mass and function in HIV-infected patients. Until now, thymic function has not been investigated in adult GH deficiency (AGHD). The objective of this clinical study was to evaluate thymic function in AGHD, as well as the repercussion upon thymopoiesis of GH treatment for restoration of GH/IGF-1 physiological levels.Methodology/Principal FindingsTwenty-two patients with documented AGHD were enrolled in this study. The following parameters were measured: plasma IGF-1 concentrations, signal-joint T-cell receptor excision circle (sjTREC) frequency, and sj/β TREC ratio. Analyses were performed at three time points: firstly on GH treatment at maintenance dose, secondly one month after GH withdrawal, and thirdly one month after GH resumption. After 1-month interruption of GH treatment, both plasma IGF-1 concentrations and sjTREC frequency were decreased (p<0.001). Decreases in IGF-1 and sjTREC levels were correlated (r = 0.61, p<0.01). There was also a decrease in intrathymic T cell proliferation as indicated by the reduced sj/β TREC ratio (p<0.01). One month after reintroduction of GH treatment, IGF-1 concentration and sjTREC frequency regained a level equivalent to the one before GH withdrawal. The sj/β TREC ratio also increased with GH resumption, but did not return to the level measured before GH withdrawal.ConclusionsIn patients with AGHD under GH treatment, GH withdrawal decreases thymic T cell output, as well as intrathymic T cell proliferation. These parameters of thymus function are completely or partially restored one month after GH resumption. These data indicate that the functional integrity of the somatotrope GH/IGF-1 axis is important for the maintenance of a normal thymus function in human adults.Trial RegistrationClinicalTrials.gov NTC00601419

Highlights

The thymus is the unique lymphoid organ responsible for the generation of self-tolerant and competent naive T cells, as well as of self antigen-specific natural regulatory T cells
In patients with adult GH deficiency (AGHD) under growth hormone (GH) treatment, GH withdrawal decreases thymic T cell output, as well as intrathymic T cell proliferation. These parameters of thymus function are completely or partially restored one month after GH resumption. These data indicate that the functional integrity of the somatotrope GH/insulin-like growth factor-1 (IGF-1) axis is important for the maintenance of a normal thymus function in human adults
One month after reintroduction of GH supplementation, plasma IGF-1 concentrations significantly increased in 21 out of 22 patients to reach a level, which was similar to the one measured before stopping GH treatment

Summary

Conclusions

In patients with AGHD under GH treatment, GH withdrawal decreases thymic T cell output, as well as intrathymic T cell proliferation. These parameters of thymus function are completely or partially restored one month after GH resumption. These data indicate that the functional integrity of the somatotrope GH/IGF-1 axis is important for the maintenance of a normal thymus function in human adults.

Introduction

Methods

Results

Discussion