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

Abstract

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 transgenic 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 compartment of the adaptive immune system, while it only marginally affects thymic function and T cell development.

Growth Hormone (GH) Deficient Mice With GHRH Gene Ablation Are Severely Deficient in Vaccine and Immune Responses Against Streptococcus pneumoniae

“…By FACS analysis, B220 labeling confirmed the lower percentage of CD19 B lymphocytes in KO mice compared to WT mice (Figure 6 ). Noteworthy, this result was similarly seen in lung (Figure 5 ) as observed in blood and lymph nodes ( 14 ). Among different types of B cells, the percentage of MZ and FO B cells was decreased in KO in comparison with WT mice (Figure 6 ).…”

“…The low percentage of macrophages in lung of Ghrh −/− mice could cause inability to initiate a strong early inflammatory response, as suggested by the lack of significant increase in IL-6 and IL-1β expression. Remarkably, the lower percentage of B lymphocytes and the higher percentage of T lymphocytes in KO compared to WT mice was also observed in blood, lymph node and spleen ( 14 ).…”

“…These mice are less prone to develop experimental autoimmune encephalomyelitis (EAE) and GH supplementation (but not GHRH) restores original susceptibility of EAE ( 44 ). Parameters and T cell responses of Ghrh −/− mice are not altered, but a relative B-cell lymphopenia and a severe splenic atrophy are constantly observed ( 14 ). Therefore, this study investigated vaccinal and anti-infectious responses of Ghrh −/− mice to S. pneumoniae .…”

“…In order to further define the physiological impact of somatotrope axis upon the immune system, we used a knockout (KO) mouse model resulting from a targeted generalized disruption of growth hormone-releasing hormone (GHRH) gene, which results in a dwarf phenotype due to severe GH deficiency ( 13 ). We have previously reported that Ghrh −/− mice exhibit normal thymic function and T cell development, but have a severe spleen atrophy and a decrease in B cell percentage when compared to their wild-type (WT) littermates ( 14 ). These observations prompted us to investigate the immune response of Ghrh −/− mice against T-cell independent type 2 antigens (TI-2), such as Streptococcus pneumoniae ( S. pneumoniae ) against which immune response is mainly based on B cells and antibody secretion.…”

Novel causes and consequences of overtraining syndrome: the EROS-DISRUPTORS study

“…The basic immunology panel was also independently affected by the presence of OTS, which supports the theory of involvement of the immune system in the pathophysiology of OTS. Although altered immunology panels (i.e., altered when compared with healthy athletes, but similar to those of non-athletes) may be linked to blunted hormonal responses to stress [23, 24], the immunology panel and the hormonal responses to stimulation did not exhibit linear correlations or predictions, at least for the immunologic markers analyzed in the present study: neutrophils, lymphocytes, and the neutrophil-to-lymphocyte ratio. Other mechanisms, such as an environment with chronic stressors leading to OTS may directly predict leukocyte composition [25].…”