June 2018 | Volume 9 | Article 296 1 ORIGINAL RESEARCH published: 06 June 2018 doi: 10.3389/fendo.2018.00296 Frontiers in Endocrinology | www.frontiersin.org Edited by: Lee E. Eiden, National Institutes of Health (NIH), United States Reviewed by: Frederik Jacobus Steyn, The University of Queensland, Australia Laurent Kappeler, Institut National de la Santé et de la Recherche Médicale (INSERM), France *Correspondence: Vincent Geenen vgeenen@uliege.be † Equal first and senior authors. Specialty section: This article was submitted to Neuroendocrine Science, a section of the journal Frontiers in Endocrinology Received: 05 February 2018 Accepted: 17 May 2018 Published: 06 June 2018 Citation: Bodart G, Farhat K, Renard- Charlet C, Becker G, Plenevaux A, Salvatori R, Geenen V and Martens H (2018) The Severe Deficiency of the Somatotrope GH-Releasing Hormone/Growth Hormone/ Insulin-Like Growth Factor 1 Axis of Ghrh −/− Mice Is Associated With an Important Splenic Atrophy and Relative B Lymphopenia. Front. Endocrinol. 9:296. doi: 10.3389/fendo.2018.00296 The Severe Deficiency of the Somatotrope GH-Releasing Hormone/Growth Hormone/Insulin- Like Growth Factor 1 Axis of Ghrh −/− Mice Is Associated With an Important Splenic Atrophy and Relative B Lymphopenia Gwennaelle Bodart 1† , Khalil Farhat 1† , Chantal Renard-Charlet 1 , Guillaume Becker 2 , Alain Plenevaux 2 , Roberto Salvatori 3 , Vincent Geenen 1 * † and Henri Martens 1† 1 GIGA-I 3 Center of Immunoendocrinology, GIGA Research Institute, University of Liege, Liège, Belgium, 2 Cyclotron Research Center, University of Liege, Liège, Belgium, 3 Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, The Johns Hopkins University, Baltimore, MD, United States A debate is still open about the precise control exerted by the somatotrope GH-releasing hormone (GHRH)/growth hormone (GH)/insulin-like growth factor 1 axis on the immune system. The objective of this study was to directly address this question through the use of Ghrh −/− mice that exhibit a severe deficiency of their somatotrope axis. After control backcross studies and normalization for the reduced global weight of trans- genic mice, no difference in weight and cellularity of the thymus was observed in Ghrh −/− mice when compared with C57BL/6 wild-type (WT) control mice. Similarly, no significant change was observed in frequency and number of thymic T cell subsets. In the periphery, Ghrh −/− mice exhibited an increase in T cell proportion associated with a higher frequency of sjTREC and naïve T cells. However, all Ghrh −/− mice displayed an absolute and relative splenic atrophy, in parallel with a decrease in B cell percentage. GH supplementation of transgenic mice for 6 weeks induced a significant increase in their global as well as absolute and relative splenic weight. Interestingly, the classical thymus involution following dexamethasone administration was shown to recover in WT mice more quickly than in mutant mice. Altogether, these data show that the severe somatotrope deficiency of Ghrh −/− mice essentially impacts the spleen and B compart- ment of the adaptive immune system, while it only marginally affects thymic function and T cell development. Keywords: somatotrope axis, GH-releasing hormone, growth hormone, insulin-like growth factor 1, thymus, developmental immunology Abbreviations: LN, lymph node; WT, wild-type; FSC, forward scatter; SSC, side scatter; TREC, T-cell receptor excision circle; Sj, signal joint; RT-qPCR, real-time quantitative PCR; DN, double-negative; DP, double-positive; SP, single-positive; TCM, central memory T cell; TEM, effector memory T cell; GC, glucocorticoid.