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Nature Reviews. Endocrinology Jul 2021Resident progenitor and/or stem cell populations in the adult adrenal cortex enable cortical cells to undergo homeostatic renewal and regeneration after injury. Renewal... (Review)
Review
Resident progenitor and/or stem cell populations in the adult adrenal cortex enable cortical cells to undergo homeostatic renewal and regeneration after injury. Renewal occurs predominantly in the outer layers of the adrenal gland but newly formed cells undergo centripetal migration, differentiation and lineage conversion in the process of forming the different functional steroidogenic zones. Over the past 10 years, advances in the genetic characterization of adrenal diseases and studies of mouse models with altered adrenal phenotypes have helped to elucidate the molecular pathways that regulate adrenal tissue renewal, several of which are fine-tuned via complex paracrine and endocrine influences. Moreover, the adrenal gland is a sexually dimorphic organ, and testicular androgens have inhibitory effects on cell proliferation and progenitor cell recruitment in the adrenal cortex. This Review integrates these advances, including the emerging role of sex hormones, into existing knowledge on adrenocortical cell renewal. An in-depth understanding of these mechanisms is expected to contribute to the development of novel therapies for severe endocrine diseases, for which current treatments are unsatisfactory.
Topics: Adrenal Cortex; Adrenal Gland Diseases; Animals; Cell Differentiation; Cell Self Renewal; Humans; Mice; Regeneration; Signal Transduction; Stem Cells
PubMed: 34011989
DOI: 10.1038/s41574-021-00491-4 -
Endocrinology Dec 2021The adrenal cortex is an endocrine organ organized into concentric zones that are specialized to produce specific steroid hormones essential for life. The development... (Review)
Review
The adrenal cortex is an endocrine organ organized into concentric zones that are specialized to produce specific steroid hormones essential for life. The development and maintenance of the adrenal cortex are complex, as a fetal adrenal is first formed from a common primordium with the gonads, followed by its separation in a distinct primordium, the invasion of the adrenal primordium by neural crest-derived cells to form the medulla, and finally its encapsulation. The fetal cortex is then replaced by a definitive cortex, which will establish zonation and be maintained throughout life by regeneration relying on the proliferation, centripetal migration, and differentiation of several stem/progenitor cell populations whose activities are sex-specific. Here, we highlight the advances made, using transgenic mouse models, to delineate the molecular mechanisms regulating these processes.
Topics: Adrenal Cortex; Adrenal Cortex Hormones; Animals; Cell Differentiation; Embryonic Development; Humans; Mice; Mice, Transgenic; Models, Animal; Organogenesis; Regeneration
PubMed: 34473283
DOI: 10.1210/endocr/bqab187 -
Clinics (Sao Paulo, Brazil) Sep 2018This review summarizes key knowledge regarding the development, growth, and growth disorders of the adrenal cortex from a molecular perspective. The adrenal gland... (Review)
Review
This review summarizes key knowledge regarding the development, growth, and growth disorders of the adrenal cortex from a molecular perspective. The adrenal gland consists of two distinct regions: the cortex and the medulla. During embryological development and transition to the adult adrenal gland, the adrenal cortex acquires three different structural and functional zones. Significant progress has been made in understanding the signaling and molecules involved during adrenal cortex zonation. Equally significant is the knowledge obtained regarding the action of peptide factors involved in the maintenance of zonation of the adrenal cortex, such as peptides derived from proopiomelanocortin processing, adrenocorticotropin and N-terminal proopiomelanocortin. Findings regarding the development, maintenance and growth of the adrenal cortex and the molecular factors involved has improved the scientific understanding of disorders that affect adrenal cortex growth. Hypoplasia, hyperplasia and adrenocortical tumors, including adult and pediatric adrenocortical adenomas and carcinomas, are described together with findings regarding molecular and pathway alterations. Comprehensive genomic analyses of adrenocortical tumors have shown gene expression profiles associated with malignancy as well as methylation alterations and the involvement of miRNAs. These findings provide a new perspective on the diagnosis, therapeutic possibilities and prognosis of adrenocortical disorders.
Topics: Adrenal Cortex; Adrenal Cortex Diseases; Embryonic Development; Humans
PubMed: 30208164
DOI: 10.6061/clinics/2018/e473s -
Molecular and Cellular Endocrinology Jun 2015The adrenal cortex plays essential roles in the control of sodium and water homeostasis, stress response, inflammation and metabolism, through secretion of... (Review)
Review
The adrenal cortex plays essential roles in the control of sodium and water homeostasis, stress response, inflammation and metabolism, through secretion of glucocorticoids and mineralocorticoids. Coordinated production of these hormones relies on functional zonation of the cortex, characterised by expression of Cyp11b2 under the control of angiotensin II and plasma potassium level in zona glomerulosa (ZG) and Cyp11b1 under the control of ACTH in zona fasciculata (ZF). The mechanisms involved in the establishment of functional zonation and its maintenance during centripetal cortex cell renewal are still poorly understood. Here, we hypothesise that the hormonal and signalling pathways that control adrenal cortex function are also involved in cortical zonation. In particular, we summarise evidence on the role of WNT/β-catenin signalling in ZG differentiation and how tight control of its activity is required to shape the adult cortex. In this context, we discuss the potential role of known WNT regulators and the possibility of a reciprocal cross-talk between PKA and WNT signalling.
Topics: Adrenal Cortex; Animals; Cell Self Renewal; Homeostasis; Humans; Models, Biological; Signal Transduction; Wnt Proteins
PubMed: 25542843
DOI: 10.1016/j.mce.2014.12.014 -
Molecular and Cellular Endocrinology Feb 2017The adult adrenal cortex is organized into concentric zones, each specialized to produce distinct steroid hormones. Cellular composition of the cortex is highly dynamic... (Review)
Review
The adult adrenal cortex is organized into concentric zones, each specialized to produce distinct steroid hormones. Cellular composition of the cortex is highly dynamic and subject to diverse signaling controls. Cortical homeostasis and regeneration rely on centripetal migration of steroidogenic cells from the outer to the inner cortex, which is accompanied by direct conversion of zona glomerulosa (zG) into zona fasciculata (zF) cells. Given the important impact of tissue structure and growth on steroidogenic function, it is essential to understand the mechanisms governing adrenal zonation and homeostasis. Towards this end, we review the distinctions between each zone by highlighting their morphological and ultra-structural features, discuss key signaling pathways influencing zonal identity, and evaluate current evidence for long-term self-renewing stem cells in the adult cortex. Finally, we review data supporting zG-to-zF transdifferentiation/direct conversion as a major mechanism of adult cortical renewal.
Topics: Adrenal Cortex; Animals; Cell Self Renewal; Homeostasis; Humans; Models, Biological; Signal Transduction
PubMed: 27619404
DOI: 10.1016/j.mce.2016.09.003 -
Endocrinology and Metabolism Clinics of... Jun 2015The human adult adrenal cortex is composed of the zona glomerulosa (zG), zona fasciculata (zF), and zona reticularis (zR), which are responsible for production of... (Review)
Review
The human adult adrenal cortex is composed of the zona glomerulosa (zG), zona fasciculata (zF), and zona reticularis (zR), which are responsible for production of mineralocorticoids, glucocorticoids, and adrenal androgens, respectively. The final completion of cortical zonation in humans does not occur until puberty with the establishment of the zR and its production of adrenal androgens; a process called adrenarche. The maintenance of the adrenal cortex involves the centripetal displacement and differentiation of peripheral Sonic hedgehog-positive progenitors cells into zG cells that later transition to zF cells and subsequently zR cells.
Topics: Adrenal Cortex; Androgens; Cell Differentiation; Glucocorticoids; Hedgehog Proteins; Humans; Mineralocorticoids; Puberty; Stem Cells; Zona Fasciculata; Zona Glomerulosa; Zona Reticularis
PubMed: 26038200
DOI: 10.1016/j.ecl.2015.02.001 -
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 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 -
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 -
Neuro Endocrinology Letters Jun 2005It is well known that plasma levels of dehydroepiandrosterone (DHEA), a steroid hormone secreted by zona reticularis (ZR) of the adrenal cortex, reach the maximal values... (Review)
Review
It is well known that plasma levels of dehydroepiandrosterone (DHEA), a steroid hormone secreted by zona reticularis (ZR) of the adrenal cortex, reach the maximal values in the third decade of life and then gradually decline with age. Moreover, the DHEA deficiency is probably responsible for several functional disturbances connected with aging. It was also found that ZR reaches its definitive volume at puberty and undergoes selective atrophy during the aging. Thus, the decline of DHEA may be a simple consequence of ZR atrophy in aged subjects. A hypothesis presented here attempts to explain the mechanism of the age-related ZR atrophy and is based on the adrenal cortex cell kinetics. In the adrenal cortex the cell proliferation indices are lower when we pass from zona glomerulosa (ZG) to the inner zones and are the lowest in ZR. In contrast, the apoptotic index is the highest in ZR. It is suggested that adrenocortical cells renew from the progenitor cells located in ZG /zona fasculata boundary and /or in subcapsular layer. These cells migrate centripetally undergoing the subsequent steps of differention and consecutive divisions - and - if not die en route - reach the most central localization in ZR. In consequence, ZR includes the "oldest" adrenocortical cells which probably in majority reached the "Hayflick's number" and cannot divide. This results in the preponderance of apoptosis over proliferation leading to progressive ZR atrophy followed by a decline of secretion of ZR-derived steroid hormones.
Topics: Adrenal Cortex; Animals; Biological Clocks; Cellular Senescence; Humans
PubMed: 15990720
DOI: No ID Found