Adrenal cortex–medulla interactions in adaptation to stress and disease

Bornstein, Stefan R.; Berger, Ilona; Scriba, Laura D; Santambrogio, Alice; Steenblock, Charlotte

doi:10.1016/j.coemr.2019.06.005

Cited by 12 publications

(5 citation statements)

References 47 publications

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“…In general, stress is defined as a challenge to an individual's homeostasis [ 34 ]. The bidirectional interplay between obesity as a form of stress and altered HPA function during the development of obesity makes it difficult to diagnose a cause or consequence.…”

Section: Discussionmentioning

confidence: 99%

“…These epigenetic changes were also suggested to occur in stem cells [ 31 , 32 ]. Adult stem and progenitor cells exist in different components of the brain-metabolic axis and are suggested to play an important role in organ maintenance and plasticity in response to changing neural stimuli and physiological needs [ [33] , [34] , [35] , [36] ]. However, the role of adult stem cells and progenitors in metabolic disease remains unknown.…”

Section: Introductionmentioning

confidence: 99%

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Insulin and obesity transform hypothalamic-pituitary-adrenal axis stemness and function in a hyperactive state

Werdermann

Berger

Scriba

et al. 2021

Molecular Metabolism

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Objective Metabolic diseases are an increasing problem in society with the brain-metabolic axis as a master regulator of the human body for sustaining homeostasis under metabolic stress. However, metabolic inflammation and disease will trigger sustained activation of the hypothalamic-pituitary-adrenal axis. In this study, we investigated the role of metabolic stress on progenitor cells in the hypothalamic-pituitary-adrenal axis. Methods In vitro , we applied insulin and leptin to murine progenitor cells isolated from the pituitary and adrenal cortex and examined the role of these hormones on proliferation and differentiation. In vivo , we investigated two different mouse models of metabolic disease, obesity in leptin-deficient ob/ob mice and obesity achieved via feeding with a high-fat diet. Results Insulin was shown to lead to enhanced proliferation and differentiation of both pituitary and adrenocortical progenitors. No alterations in the progenitors were noted in our chronic metabolic stress models. However, hyperactivation of the hypothalamic-pituitary-adrenal axis was observed and the expression of the appetite-regulating genes Npy and Agrp changed in both the hypothalamus and adrenal. Conclusions It is well-known that chronic stress and stress hormones such as glucocorticoids can induce metabolic changes including obesity and diabetes. In this article, we show for the first time that this might be based on an early sensitization of stem cells of the hypothalamic-pituitary-adrenal axis. Thus, pituitary and adrenal progenitor cells exposed to high levels of insulin are metabolically primed to a hyper-functional state leading to enhanced hormone production. Likewise, obese animals exhibit a hyperactive hypothalamic-pituitary-adrenal axis leading to adrenal hyperplasia. This might explain how stress in early life can increase the risk for developing metabolic syndrome in adulthood.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Insulin and obesity transform hypothalamic-pituitary-adrenal axis stemness and function in a hyperactive state

Werdermann

Berger

Scriba

et al. 2021

Molecular Metabolism

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“…It is known that cortisol secreted by the adrenal glands acts on the pancreas to increase glucagon release and reduce insulin release [40]. Furthermore, it is known that the adrenal cortex and the adrenal medulla regulate the release of cortisol and adrenaline, respectively, in a synchronised bidirectional manner [41,42]. Given the fact that hypoglycaemic states increase the release of adrenaline from the adrenal medulla, this likely directly stimulates the release of cortisol from the adrenal cortex.…”

Section: Pancreatic Responses To Hypoglycaemia and The Relevance Of T...mentioning

confidence: 99%

Role of the Adrenal Medulla in Hypoglycaemia-Associated Autonomic Failure—A Diabetic Perspective

Senthilkumaran,

Koch,

Herselman

et al. 2024

Metabolites

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Hypoglycaemia-associated autonomic failure (HAAF) is characterised by an impairment in adrenal medullary and neurogenic symptom responses following episodes of recurrent hypoglycaemia. Here, we review the status quo of research related to the regulatory mechanisms of the adrenal medulla in its response to single and recurrent hypoglycaemia in both diabetic and non-diabetic subjects with particular focus given to catecholamine synthesis, enzymatic activity, and the impact of adrenal medullary peptides. Short-term post-transcriptional modifications, particularly phosphorylation at specific residues of tyrosine hydroxylase (TH), play a key role in the regulation of catecholamine synthesis. While the effects of recurrent hypoglycaemia on catecholamine synthetic enzymes remain inconsistent, long-term changes in TH protein expression suggest species-specific responses. Adrenomedullary peptides such as neuropeptide Y (NPY), galanin, and proenkephalin exhibit altered gene and protein expression in response to hypoglycaemia, suggesting a potential role in the modulation of catecholamine secretion. Of note is NPY, since its antagonism has been shown to prevent reductions in TH protein expression. This review highlights the need for further investigation into the molecular mechanisms involved in the adrenal medullary response to hypoglycaemia. Despite advancements in our understanding of HAAF in non-diabetic rodents, a reliable diabetic rodent model of HAAF remains a challenge.

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“…A complex network of autocrine and paracrine pathways regulates steroid and catecholamine biosynthesis/secretion [4]. Bidirectional cross-talk between the adrenal cortex and the medulla is furthermore involved in the regulation of both hormone systems (▶ Fig.…”

Section: Introductionmentioning

confidence: 99%

Adrenal Hormone Interactions and Metabolism: A Single Sample Multi-Omics Approach

et al. 2021

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The adrenal gland is important for many physiological and pathophysiological processes, but studies are often restricted by limited availability of sample material. Improved methods for sample preparation are needed to facilitate analyses of multiple classes of adrenal metabolites and macromolecules in a single sample. A procedure was developed for preparation of chromaffin cells, mouse adrenals, and human chromaffin tumors that allows for multi-omics analyses of different metabolites and preservation of native proteins. To evaluate the new procedure, aliquots of samples were also prepared using conventional procedures. Metabolites were analyzed by liquid-chromatography with mass spectrometry or electrochemical detection. Metabolite contents of chromaffin cells and tissues analyzed with the new procedure were similar or even higher than with conventional methods. Catecholamine contents were comparable between both procedures. The TCA cycle metabolites, cis-aconitate, isocitate, and α-ketoglutarate were detected at higher concentrations in cells, while in tumor tissue only isocitrate and potentially fumarate were measured at higher contents. In contrast, in a broad untargeted metabolomics approach, a methanol-based preparation procedure of adrenals led to a 1.3-fold higher number of detected metabolites. The established procedure also allows for simultaneous investigation of adrenal hormones and related enzyme activities as well as proteins within a single sample. This novel multi-omics approach not only minimizes the amount of sample required and overcomes problems associated with tissue heterogeneity, but also provides a more complete picture of adrenal function and intra-adrenal interactions than previously possible.

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Adrenal cortex–medulla interactions in adaptation to stress and disease

Cited by 12 publications

References 47 publications

Insulin and obesity transform hypothalamic-pituitary-adrenal axis stemness and function in a hyperactive state

Insulin and obesity transform hypothalamic-pituitary-adrenal axis stemness and function in a hyperactive state

Role of the Adrenal Medulla in Hypoglycaemia-Associated Autonomic Failure—A Diabetic Perspective

Adrenal Hormone Interactions and Metabolism: A Single Sample Multi-Omics Approach

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