ACTH controls thymocyte homeostasis independent of glucocorticoids

Talaber, Gergely; Tuckermann, Jan; Okret, Sam

doi:10.1096/fj.14-268508

Cited by 28 publications

(13 citation statements)

References 43 publications

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“…Adrenalectomized mice treated with ACTH under conditions repressing endogenous ACTH secretion exhibit an increase in the number of thymocytes and splenic naive T-cells compared with control animals. These results show that ACTH directly controls thymocyte homeostasis independently of circulating GC (Talaber et al 2015).…”

Section: Acth and Thymus Growthmentioning

confidence: 55%

60 YEARS OF POMC: Adrenal and extra-adrenal functions of ACTH

Gallo‐Payet

2016

Journal of Molecular Endocrinology

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The pituitary adrenocorticotropic hormone (ACTH) plays a pivotal role in homeostasis and stress response and is thus the major component of the hypothalamo–pituitary–adrenal axis. After a brief summary of ACTH production from proopiomelanocortin (POMC) and on ACTH receptor properties, the first part of the review covers the role of ACTH in steroidogenesis and steroid secretion. We highlight the mechanisms explaining the differential acute vs chronic effects of ACTH on aldosterone and glucocorticoid secretion. The second part summarizes the effects of ACTH on adrenal growth, addressing its role as either a mitogenic or a differentiating factor. We then review the mechanisms involved in steroid secretion, from the classical Cyclic adenosine monophosphate second messenger system to various signaling cascades. We also consider how the interaction between the extracellular matrix and the cytoskeleton may trigger activation of signaling platforms potentially stimulating or repressing the steroidogenic potency of ACTH. Finally, we consider the extra-adrenal actions of ACTH, in particular its role in differentiation in a variety of cell types, in addition to its known lipolytic effects on adipocytes. In each section, we endeavor to correlate basic mechanisms of ACTH function with the pathological consequences of ACTH signaling deficiency and of overproduction of ACTH.

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Section: Acth and Thymus Growthmentioning

confidence: 55%

60 YEARS OF POMC: Adrenal and extra-adrenal functions of ACTH

Gallo‐Payet

2016

Journal of Molecular Endocrinology

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“…118,119 The adrencorticotropic hormone receptor, melanocortin receptor subtype 2, is expressed on TECs and its activation regulates thymo cyte expansion when the systemic concentration of glucocorticoid is low. 120 The intrathymic production of corticotropinreleasing factor by thymocytes has also been reported. 121 Taken together, these findings suggest that a circuitry, similar to that seen in the hypothalamus-pituitaryadrenal axis, might also occur within the thymus, but this system needs to be investigated further.…”

Section: Sex Hormonesmentioning

confidence: 96%

Hormonal control of T-cell development in health and disease

et al. 2015

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The physiology of the thymus, the primary lymphoid organ in which T cells are generated, is controlled by hormones. Data from animal models indicate that several peptide and nonpeptide hormones act pleiotropically within the thymus to modulate the proliferation, differentiation, migration and death by apoptosis of developing thymocytes. For example, growth hormone and prolactin can enhance thymocyte proliferation and migration, whereas glucocorticoids lead to the apoptosis of these developing cells. The thymus undergoes progressive age-dependent atrophy with a loss of cells being generated and exported, therefore, hormone-based therapies are being developed as an alternative strategy to rejuvenate the organ, as well as to augment thymocyte proliferation and the export of mature T cells to peripheral lymphoid organs. Some hormones (such as growth hormone and progonadoliberin-1) are also being used as therapeutic agents to treat immunodeficiency disorders associated with thymic atrophy, such as HIV infection. In this Review, we discuss 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.

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“…There is also evidence for ACTH receptors on lymphocytes (70), although the functional significance of this remains difficult to ascertain. More recently, it has been shown that ACTH controls growth of the thymus and that this is not via stimulation by glucocorticoids (392).…”

Section: Role Of Acth In Lymphocytesmentioning

confidence: 99%

POMC: The Physiological Power of Hormone Processing

Harno

Ramamoorthy

Coll

et al. 2018

Physiological Reviews

144

120

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Pro-opiomelanocortin (POMC) is the archetypal polypeptide precursor of hormones and neuropeptides. In this review, we examine the variability in the individual peptides produced in different tissues and the impact of the simultaneous presence of their precursors or fragments. We also discuss the problems inherent in accurately measuring which of the precursors and their derived peptides are present in biological samples. We address how not being able to measure all the combinations of precursors and fragments quantitatively has affected our understanding of the pathophysiology associated with POMC processing. To understand how different ratios of peptides arise, we describe the role of the pro-hormone convertases (PCs) and their tissue specificities and consider the cellular processing pathways which enable regulated secretion of different peptides that play crucial roles in integrating a range of vital physiological functions. In the pituitary, correct processing of POMC peptides is essential to maintain the hypothalamic-pituitary-adrenal axis, and this processing can be disrupted in POMC-expressing tumors. In hypothalamic neurons expressing POMC, abnormalities in processing critically impact on the regulation of appetite, energy homeostasis, and body composition. More work is needed to understand whether expression of the POMC gene in a tissue equates to release of bioactive peptides. We suggest that this comprehensive view of POMC processing, with a focus on gaining a better understanding of the combination of peptides produced and their relative bioactivity, is a necessity for all involved in studying this fascinating physiological regulatory phenomenon.

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ACTH controls thymocyte homeostasis independent of glucocorticoids

Cited by 28 publications

References 43 publications

60 YEARS OF POMC: Adrenal and extra-adrenal functions of ACTH

60 YEARS OF POMC: Adrenal and extra-adrenal functions of ACTH

Hormonal control of T-cell development in health and disease

POMC: The Physiological Power of Hormone Processing

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