Growth hormone – thymus function
A recent PLoS One study by Gabriel Morrhaye et al., demonstrates that the functional integrity of the somatotrope growth hormone/insulin-like growth factor-1 axis is important for the maintenance of a normal thymus function in human adults.
The secretion of growth hormone (GH) declines with aging until only low levels can be detected in individuals aged ≥60 years. Recent evidence also indicates that infusion in old mice of ghrelin, a GH secretagogue, significantly improves thymopoiesis, whereas GH treatment may reverse thymic atrophy and enhance the number of circulating naive CD4 T cells in HIV-infected adults.
The PLoS One study shows that, in patients with well-documented GH deficiency, both the frequency of circulating sjTRECs (marker of thymic T cell output) in PBMCs and the sj/bTREC ratio (marker of intrathymic precursor T cell proliferation) are significantly decreased one month after GH withdrawal.
Resumption of GH treatment for one month is sufficient to increase thymic T cell output to a level similar or close to the one measured before GH interruption.
The authors suggest that the use of GH and/or GH secretagogues should be considered in the future for restoring an important set of thymic functions that are compromised by aging.
SOURCE: PLoS One 2009, 4:e5668
Updates
A 2012 study by Hamid Kermani et al. addressed the question of the expression and the role of the growth hormone/insulin-like growth factor (GH/IGF) axis in the thymus. The study demonstrated that the thymotropic properties of the somatotrope GH/IGF-1 axis involve an interaction between exogenous GH and GHR expressed by TEC. Since thymic IGF-1 is not increased by GH treatment, the effects of GH upon T cell differentiation could implicate a different local growth factor or cytokine.
A 2016 review article by Katsuiku Hirokawa, Masanori Utsuyama and Yuko Kikuchi indicates that GH is necessary for the development of thymus dependent immune system but GH deficiency is favorable for long life span and decreases occurrence of cancer and DM. This situation is a kind of trade off situation between the immune system and GH. Thus the early decline of high level of GH occurring shortly after the birth is a cause of early decline of thymic functions, but favorable for longer lifespan. This situation could be a kind of trade off situation between thymus and GH.
Another 2016 review by Wilson Savino et al. discusses the accumulating data that shows the thymus gland is under complex and multifaceted hormonal control that affects the process of T-cell development in health and disease. Thus, microenvironmental cells in the thymus constitutively produce hormones that are typically secreted by the pituitary gland, such as growth hormone, prolactin, oxytocin and vasopressin
Glucocorticoids induce thymocyte depletion through caspase-dependent apoptosis, whereas growth hormone enhances thymocyte proliferation and migration. Considering the variety of the interactions between the endocrine, the nervous and the immune systems, dysfunctions in one of these systems can affect the other.
A 2021 study by Marvin Paulo Lins et al. evaluated the influence of GH on the interactions between mature thymocytes and the thymic endothelium involved in the migratory process. In the transendothelial migration assay, a large number of GH-treated thymocytes, mainly the CD4–CD8+ subset, migrated towards the endothelium under the stimulus of insulin-like growth factor 1. Thus, the authors demonstrated the positive actions of GH in thymocyte/thymic endothelium interactions, including transendothelial migration.
A 2021 review by Andrzej Bartke et al. indicates that treatment of healthy men with a combination of GH, dehydroepiandrosterone, and metformin was reported to restore thymus function and reduce epigenetic age. Studies of human subjects with deficiency of GH or GH receptors and studies of mice with the same endocrine syndromes identified several phenotypic changes related (positively or negatively) to the previously reported predisposition to healthy aging. Results of these and other recent studies advance present understanding of the mechanisms by which GH influences aging and longevity and of the trade-offs involved.
Interestingly, novel findings described in this section add to the evidence for the existence of both beneficial and detrimental effects of suppression of GH actions. These findings also support the notion that various trade-offs are involved in the impact of somatotropic signaling on the life history, including the trajectory of aging. Coexistence of beneficial and detrimental effects of a particular factor (in this case, GH) on different facets or different mechanisms of the same process (in this case, aging) would seem to fit a novel concept of “antagonistic antagonistic heterogeneity.” Antagonistic heterogeneity refers to coexistence of positive and negative correlation of the same genetic variant with traits that are directly correlated with each other.