The Somatotrope Growth Hormone-Releasing Hormone/Growth Hormone/Insulin-Like Growth Factor-1 Axis in Immunoregulation and Immunosenescence

Bodart, Gwennaëlle; Farhat, Khalil; Charlet-Renard, Chantal; Salvatori, Roberto; Geenen, Vincent; Martens, Henri

doi:10.1159/000452913

Cited by 18 publications

(10 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Intriguingly, the GH–IGF1 axis and the immune system seem to be finely interconnected. In fact, it is worth recalling that GH is fundamental for the development and maintenance of the immune system, and its reduction might also lead to an immune system disruption, as recently observed in rodent models (10). Moreover, both GH and IGF1 are capable of stimulating the development of antigen‐responsive clones of B and T cells, and they can increase the survival of antigen‐responsive cells (10).…”

mentioning

confidence: 89%

“…In fact, it is worth recalling that GH is fundamental for the development and maintenance of the immune system, and its reduction might also lead to an immune system disruption, as recently observed in rodent models (10). Moreover, both GH and IGF1 are capable of stimulating the development of antigen‐responsive clones of B and T cells, and they can increase the survival of antigen‐responsive cells (10). Some reports have also indicated that GH drives macrophage polarization toward an M2 anti‐inflammatory phenotype (11), and it has been suggested that the somatotropic axis may play an important role in the regulation of stressful conditions such as sepsis or infective and inflammatory diseases (9).…”

mentioning

confidence: 89%

See 1 more Smart Citation

Is Growth Hormone Insufficiency the Missing Link Between Obesity, Male Gender, Age, and COVID‐19 Severity?

Lubrano

Masi

Risi

et al. 2020

Obesity

View full text Add to dashboard Cite

Evidence has emerged regarding an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) with worse prognosis in elderly male patients with obesity, and blunted growth hormone (GH) secretion represents a feature of this population subgroup. Here, a comprehensive review of the possible links between GH–insulinlike growth factor 1 axis impairment and coronavirus disease 2019 (COVID‐19) severity is offered. First, unequivocal evidence suggests that immune system dysregulation represents a key element in determining SARS‐CoV‐2 severity, as well as the association with adult‐onset GH deficiency (GHD); notably, if GH is physiologically involved in the development and maintenance of the immune system, its pharmacological replacement in GHD patients seems to positively influence their inflammatory status. In addition, the impaired fibrinolysis associated with GHD may represent a further link between GH–insulin‐like growth factor 1 axis impairment and COVID‐19 severity, as it has been associated with both conditions. In conclusion, several sources of evidence have supported a relationship between GHD and COVID‐19, and they also shed light upon potential beneficial effects of recombinant GH treatment on COVID‐19 patients.

show abstract

mentioning

confidence: 89%

mentioning

confidence: 89%

Is Growth Hormone Insufficiency the Missing Link Between Obesity, Male Gender, Age, and COVID‐19 Severity?

Lubrano

Masi

Risi

et al. 2020

Obesity

View full text Add to dashboard Cite

show abstract

“…This was reinforced by the observation of aged-atrophic thymus rejuvenation by GH-producing pituitary adenoma cells ( 5 ). The effects mediated by GH and IGF1 on immune cells have been extensively reviewed ( 6 , 7 ).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…In the immune system, GH stimulates the growth of primary and secondary lymphoid organs [7,8], where it induces lymphocyte proliferation and the production of cytokines and other immune factors [9,10]. In addition, GH also acts as a cytokine [11] and stimulates the innate and adaptative immune responses [12]. Moreover, GH is expressed in immune cells of various species, such as canine lymph nodes [13], human peripheral blood lymphocytes [14], rat, mouse, and bovine splenocytes [15,16], as well as in several immune cell lines (H-9 T cells and IM-9 B cells) [17].…”

Section: Introductionmentioning

confidence: 99%

Thyrotropin-Releasing Hormone (TRH) and Somatostatin (SST), but not Growth Hormone-Releasing Hormone (GHRH) nor Ghrelin (GHRL), Regulate Expression and Release of Immune Growth Hormone (GH) from Chicken Bursal B-Lymphocyte Cultures

Pech-Pool

Berumen

Martínez-Moreno

et al. 2020

IJMS

View full text Add to dashboard Cite

It is known that growth hormone (GH) is expressed in immune cells, where it exerts immunomodulatory effects. However, the mechanisms of expression and release of GH in the immune system remain unclear. We analyzed the effect of growth hormone-releasing hormone (GHRH), thyrotropin-releasing hormone (TRH), ghrelin (GHRL), and somatostatin (SST) upon GH mRNA expression, intracellular and released GH, Ser133-phosphorylation of CREB (pCREBS133), intracellular Ca2+ levels, as well as B-cell activating factor (BAFF) mRNA expression in bursal B-lymphocytes (BBLs) cell cultures since several GH secretagogues, as well as their corresponding receptors (-R), are expressed in B-lymphocytes of several species. The expression of TRH/TRH-R, ghrelin/GHS-R1a, and SST/SST-Rs (Subtypes 1 to 5) was observed in BBLs by RT-PCR and immunocytochemistry (ICC), whereas GHRH/GHRH-R were absent in these cells. We found that TRH treatment significantly increased local GH mRNA expression and CREB phosphorylation. Conversely, SST decreased GH mRNA expression. Additionally, when added together, SST prevented TRH-induced GH mRNA expression, but no changes were observed in pCREBS133 levels. Furthermore, TRH stimulated GH release to the culture media, while SST increased the intracellular content of this hormone. Interestingly, SST inhibited TRH-induced GH release in a dose-dependent manner. The coaddition of TRH and SST decreased the intracellular content of GH. After 10 min. of incubation with either TRH or SST, the intracellular calcium levels significantly decreased, but they were increased at 60 min. However, the combined treatment with both peptides maintained the Ca2+ levels reduced up to 60-min. of incubation. On the other hand, BAFF cytokine mRNA expression was significantly increased by TRH administration. Altogether, our results suggest that TRH and SST are implicated in the regulation of GH expression and release in BBL cultures, which also involve changes in pCREBS133 and intracellular Ca2+ concentration. It is likely that TRH, SST, and GH exert autocrine/paracrine immunomodulatory actions and participate in the maturation of chicken BBLs.

show abstract

The Somatotrope Growth Hormone-Releasing Hormone/Growth Hormone/Insulin-Like Growth Factor-1 Axis in Immunoregulation and Immunosenescence

Cited by 18 publications

References 54 publications

Is Growth Hormone Insufficiency the Missing Link Between Obesity, Male Gender, Age, and COVID‐19 Severity?

Is Growth Hormone Insufficiency the Missing Link Between Obesity, Male Gender, Age, and COVID‐19 Severity?

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

Thyrotropin-Releasing Hormone (TRH) and Somatostatin (SST), but not Growth Hormone-Releasing Hormone (GHRH) nor Ghrelin (GHRL), Regulate Expression and Release of Immune Growth Hormone (GH) from Chicken Bursal B-Lymphocyte Cultures

Contact Info

Product

Resources

About