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British Medical Journal Apr 1955
Topics: Adrenal Cortex; Adrenal Cortex Hormones; Humans; Hyperaldosteronism
PubMed: 14351805
DOI: 10.1136/bmj.1.4917.851-b -
Molecular and Cellular Endocrinology Jan 2021The adrenal cortex functions to produce steroid hormones necessary for life. To maintain its functional capacity throughout life, the adrenal cortex must be continually... (Review)
Review
The adrenal cortex functions to produce steroid hormones necessary for life. To maintain its functional capacity throughout life, the adrenal cortex must be continually replenished and rapidly repaired following injury. Moreover, the adrenal responds to endocrine-mediated organismal needs, which are highly dynamic and necessitate a precise steroidogenic response. To meet these diverse needs, the adrenal employs multiple cell populations with stem cell function. Here, we discuss the literature on adrenocortical stem cells using hematopoietic stem cells as a benchmark to examine the functional capacity of particular cell populations, including those located in the capsule and peripheral cortex. These populations are coordinately regulated by paracrine and endocrine signaling mechanisms, and display remarkable plasticity to adapt to different physiological and pathological conditions. Some populations also exhibit sex-specific activity, which contributes to highly divergent proliferation rates between sexes. Understanding mechanisms that govern adrenocortical renewal has broad implications for both regenerative medicine and cancer.
Topics: Adrenal Cortex; Animals; Cell Plasticity; Female; Humans; Male; Models, Biological; Sex Characteristics; Stem Cells; Wnt Signaling Pathway
PubMed: 33058950
DOI: 10.1016/j.mce.2020.111043 -
Molecular and Cellular Endocrinology Mar 2012The human adrenal cortex secretes mineralocorticoids, glucocorticoids and adrenal androgens. These steroids are produced from unique cell types located within the three... (Review)
Review
The human adrenal cortex secretes mineralocorticoids, glucocorticoids and adrenal androgens. These steroids are produced from unique cell types located within the three distinct zones of the adrenal cortex. Disruption of adrenal steroid production results in a variety of diseases that can lead to hypertension, metabolic syndrome, infertility and androgen excess. The adrenal cortex is also a common site for the development of adenomas, and rarely the site for the development of carcinomas. The adenomas can lead to diseases associated with adrenal steroid excess, while the carcinomas are particularly aggressive and have a poor prognosis. In vitro cell culture models provide important tools to examine molecular and cellular mechanisms controlling both the normal and pathologic function of the adrenal cortex. Herein, we discuss currently available human adrenocortical carcinoma cell lines and their use as model systems for adrenal studies.
Topics: Adenoma; Adrenal Cortex; Adrenal Cortex Neoplasms; Androgens; Cell Line, Tumor; Glucocorticoids; Humans; Mineralocorticoids; Models, Biological
PubMed: 21924324
DOI: 10.1016/j.mce.2011.08.041 -
Molecular and Cellular Endocrinology Apr 2017The adrenal cortex is a dynamic tissue responsible for the synthesis of steroid hormones, including mineralocorticoids, glucocorticoids, and androgens in humans.... (Review)
Review
The adrenal cortex is a dynamic tissue responsible for the synthesis of steroid hormones, including mineralocorticoids, glucocorticoids, and androgens in humans. Advances have been made in understanding the role of adrenocortical stem/progenitor cell populations in cortex homeostasis and self-renewal. Recently, large molecular profiling studies of adrenocortical carcinoma (ACC) have given insights into proteins and signaling pathways involved in normal tissue homeostasis that become dysregulated in cancer. These data provide an impetus to examine the cellular pathways implicated in adrenocortical disease and study connections, or lack thereof, between adrenal homeostasis and tumorigenesis, with a particular focus on stem and progenitor cell pathways. In this review, we discuss evidence for stem/progenitor cells in the adrenal cortex, proteins and signaling pathways that may regulate these cells, and the role these proteins play in pathologic and neoplastic conditions. In turn, we also examine common perturbations in adrenocortical tumors (ACT) and how these proteins and pathways may be involved in adrenal homeostasis.
Topics: Adrenal Cortex; Adrenal Cortex Neoplasms; Hedgehog Proteins; Humans; Stem Cells; Wnt Signaling Pathway
PubMed: 27940298
DOI: 10.1016/j.mce.2016.12.005 -
Cells Dec 2021Cellular senescence is considered a physiological process along with aging and has recently been reported to be involved in the pathogenesis of many age-related... (Review)
Review
Cellular senescence is considered a physiological process along with aging and has recently been reported to be involved in the pathogenesis of many age-related disorders. Cellular senescence was first found in human fibroblasts and gradually explored in many other organs, including endocrine organs. The adrenal cortex is essential for the maintenance of blood volume, carbohydrate metabolism, reaction to stress and the development of sexual characteristics. Recently, the adrenal cortex was reported to harbor some obvious age-dependent features. For instance, the circulating levels of aldosterone and adrenal androgen gradually descend, whereas those of cortisol increase with aging. The detailed mechanisms have remained unknown, but cellular senescence was considered to play an essential role in age-related changes of the adrenal cortex. Recent studies have demonstrated that the senescent phenotype of zona glomerulosa (ZG) acts in association with reduced aldosterone production in both physiological and pathological aldosterone-producing cells, whereas senescent cortical-producing cells seemed not to have a suppressed cortisol-producing ability. In addition, accumulated lipofuscin formation, telomere shortening and cellular atrophy in zona reticularis cells during aging may account for the age-dependent decline in adrenal androgen levels. In adrenocortical disorders, including both aldosterone-producing adenoma (APA) and cortisol-producing adenoma (CPA), different cellular subtypes of tumor cells presented divergent senescent phenotypes, whereby compact cells in both APA and CPA harbored more senescent phenotypes than clear cells. Autonomous cortisol production from CPA reinforced a local cellular senescence that was more severe than that in APA. Adrenocortical carcinoma (ACC) was also reported to harbor oncogene-induced senescence, which compensatorily follows carcinogenesis and tumor progress. Adrenocortical steroids can induce not only a local senescence but also a periphery senescence in many other tissues. Therefore, herein, we systemically review the recent advances related to cellular senescence in adrenocortical biology and its associated disorders.
Topics: Adrenal Cortex; Adrenal Cortex Neoplasms; Aging; Aldosterone; Androgens; Cellular Senescence; Humans; Hydrocortisone; Zona Glomerulosa
PubMed: 34943980
DOI: 10.3390/cells10123474 -
Frontiers in Endocrinology 2021Primary adrenal insufficiency (PAI) is a rare disease and potentially fatal if unrecognized. It is characterized by destruction of the adrenal cortex, most frequently of... (Review)
Review
Primary adrenal insufficiency (PAI) is a rare disease and potentially fatal if unrecognized. It is characterized by destruction of the adrenal cortex, most frequently of autoimmune origin, resulting in glucocorticoid, mineralocorticoid, and adrenal androgen deficiencies. Initial signs and symptoms can be nonspecific, contributing to late diagnosis. Loss of zona glomerulosa function may precede zona fasciculata and reticularis deficiencies. Patients present with hallmark manifestations including fatigue, weight loss, abdominal pain, melanoderma, hypotension, salt craving, hyponatremia, hyperkalemia, or acute adrenal crisis. Diagnosis is established by unequivocally low morning serum cortisol/aldosterone and elevated ACTH and renin concentrations. A standard dose (250 µg) Cosyntropin stimulation test may be needed to confirm adrenal insufficiency (AI) in partial deficiencies. Glucocorticoid and mineralocorticoid substitution is the hallmark of treatment, alongside patient education regarding dose adjustments in periods of stress and prevention of acute adrenal crisis. Recent studies identified partial residual adrenocortical function in patients with AI and rare cases have recuperated normal hormonal function. Modulating therapies using rituximab or ACTH injections are in early stages of investigation hoping it could maintain glucocorticoid residual function and delay complete destruction of adrenal cortex.
Topics: Adrenal Cortex; Adrenal Cortex Function Tests; Adrenal Insufficiency; Aldosterone; Diagnostic Techniques, Endocrine; Humans; Hydrocortisone
PubMed: 34512551
DOI: 10.3389/fendo.2021.720769 -
The Tohoku Journal of Experimental... Apr 2021The human adrenal cortex is a complex endocrine organ that produces mineralocorticoids, glucocorticoids and androgens. These steroids are produced in distinct cell types... (Review)
Review
The human adrenal cortex is a complex endocrine organ that produces mineralocorticoids, glucocorticoids and androgens. These steroids are produced in distinct cell types located within the glomerulosa, fasciculata and reticularis of the adrenal cortex. Abnormal adrenal steroidogenesis leads to a variety of diseases that can cause hypertension, metabolic syndrome, infertility and premature adrenarche. The adrenal cortex can also develop steroid-producing adenomas and rarely adrenocortical carcinomas. In vitro cell culture models provide important tools to study molecular and cellular mechanisms controlling both the physiologic and pathologic conditions of the adrenal cortex. In addition, the presence of multiple steroid-metabolizing enzymes within adrenal cells makes it a model for defining possible endocrine disruptors that might block these enzymes. The regulation and dysregulation of human adrenal steroid production and cell division/tumor growth can be studied using freshly isolated cells but this requires access to human adrenal glands, which are not available to most investigators. Immortalized human adrenocortical cell lines have proven to be of considerable value in studying the molecular and biochemical mechanisms controlling adrenal steroidogenesis and tumorigenesis. Current human adrenal cell lines include the original NCI-H295 and its substrains: H295A, H295R, HAC13, HAC15, HAC50 and H295RA as well as the recently established MUC-1, CU-ACC1 and CU-ACC2. The current review will discuss the use of primary cultures of fetal and adult adrenal cells as well as adrenocortical cell lines as in vitro models for the study of human adrenal physiology and pathophysiology.
Topics: Adrenal Cortex; Cell Line, Tumor; Cells, Cultured; Humans; Models, Biological
PubMed: 33840647
DOI: 10.1620/tjem.253.217 -
Archives of Pathology & Laboratory... Aug 2008In surgical pathology practice adrenal cortical tumors are rare. However, in autopsy series adrenal cortical nodules are found frequently. These are now being identified... (Review)
Review
CONTEXT
In surgical pathology practice adrenal cortical tumors are rare. However, in autopsy series adrenal cortical nodules are found frequently. These are now being identified more commonly in life when the abdomen is scanned for other disease. It is important to differentiate between benign and malignant lesions as adrenal cortical carcinoma is an aggressive tumor. Molecular genetic investigations are providing new information on both pathogenesis of adrenal tumors and basic adrenal development and physiology.
OBJECTIVE
To provide an overview of current knowledge on adrenal cortical development and structure that informs our understanding of genetic diseases of the adrenal cortex and adrenal cortical tumors.
DATA SOURCES
Literature review using PubMed via the Endnote bibliography tool.
CONCLUSIONS
The understanding of basic developmental and physiologic processes permits a better understanding of diseases of the adrenal cortex. The information coming from investigation of the molecular pathology of adrenal cortical tumors is beginning to provide additional tests for the assessment of malignant potential in diagnosis but the mainstay remains traditional histologic analysis.
Topics: Adrenal Cortex; Adrenal Cortex Neoplasms; Adrenal Gland Diseases; Growth; Humans; Immunohistochemistry; Prognosis
PubMed: 18684025
DOI: 10.5858/2008-132-1263-LOTAC -
Molecular and Cellular Endocrinology Feb 2017The adrenal gland is a highly plastic organ with the capacity to adapt the body homeostasis to different physiological needs. The existence of stem-like cells in the... (Review)
Review
The adrenal gland is a highly plastic organ with the capacity to adapt the body homeostasis to different physiological needs. The existence of stem-like cells in the adrenal cortex has been revealed in many studies. Recently, we identified and characterized in mice a pool of glia-like multipotent Nestin-expressing progenitor cells, which contributes to the plasticity of the adrenal medulla. In addition, we found that these Nestin progenitors are actively involved in the stress response by giving rise to chromaffin cells. Interestingly, we also observed a Nestin-GFP-positive cell population located under the adrenal capsule and scattered through the cortex. In this article, we discuss the possibility of a common progenitor giving rise to subpopulations of cells both in the adrenal cortex and medulla, the isolation and characterization of this progenitor as well as its clinical potential in transplantation therapies and in pathophysiology.
Topics: Adaptation, Physiological; Adrenal Cortex; Animals; Chromaffin Cells; Humans; Neurodegenerative Diseases; Stem Cells; Stress, Physiological
PubMed: 27637345
DOI: 10.1016/j.mce.2016.09.011 -
Hormone and Metabolic Research =... Jan 2024Endocrine-disrupting chemicals (EDCs) are exogenous substances known to interfere with endocrine homeostasis and promote adverse health outcomes. Their impact on the... (Review)
Review
Endocrine-disrupting chemicals (EDCs) are exogenous substances known to interfere with endocrine homeostasis and promote adverse health outcomes. Their impact on the adrenal cortex, corticosteroids and their physiological role in the organism has not yet been sufficiently elucidated. In this review, we collect experimental and epidemiological evidence on adrenal disruption by relevant endocrine disruptors. In vitro data suggest significant alterations of gene expression, cell signalling, steroid production, steroid distribution, and action. Additionally, morphological studies revealed disturbances in tissue organization and development, local inflammation, and zone-specific hyperplasia. Finally, endocrine circuits, such as the hypothalamic-pituitary-adrenal axis, might be affected by EDCs. Many questions regarding the detection of steroidogenesis disruption and the effects of combined toxicity remain unanswered. Not only due to the diverse mode of action of adrenal steroids and their implication in many common diseases, there is no doubt that further research on endocrine disruption of the adrenocortical system is needed.
Topics: Adrenal Cortex; Adrenal Cortex Hormones; Endocrine Disruptors; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Steroids
PubMed: 37884032
DOI: 10.1055/a-2198-9307