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Molecular and Cellular Endocrinology May 2021The adult human adrenal cortex produces steroid hormones that are crucial for life, supporting immune response, glucose homeostasis, salt balance and sexual maturation.... (Review)
Review
The adult human adrenal cortex produces steroid hormones that are crucial for life, supporting immune response, glucose homeostasis, salt balance and sexual maturation. It consists of three histologically distinct and functionally specialized zones. The fetal adrenal forms from mesodermal material and produces predominantly adrenal C steroids from its fetal zone, which involutes after birth. Transition to the adult cortex occurs immediately after birth for the formation of the zona glomerulosa and fasciculata for aldosterone and cortisol production and continues through infancy until the zona reticularis for adrenal androgen production is formed with adrenarche. The development of this indispensable organ is complex and not fully understood. This article gives an overview of recent knowledge gained of adrenal biology from two perspectives: one, from basic science studying adrenal development, zonation and homeostasis; and two, from adrenal disorders identified in persons manifesting with various isolated or syndromic forms of primary adrenal insufficiency.
Topics: Adrenal Insufficiency; Aldosterone; Androgens; Animals; Humans; Hydrocortisone; Zona Glomerulosa; Zona Reticularis
PubMed: 33607267
DOI: 10.1016/j.mce.2021.111206 -
Molecular and Cellular Endocrinology Feb 2021The Wnt signaling pathway is a critical mediator of the development and maintenance of several tissues. The adrenal cortex is highly dependent upon Wnt/β-catenin... (Review)
Review
The Wnt signaling pathway is a critical mediator of the development and maintenance of several tissues. The adrenal cortex is highly dependent upon Wnt/β-catenin signaling for proper zonation and endocrine function. Adrenocortical cells emerge in the peripheral capsule and subcapsular cortex of the gland as progenitor cells that centripetally differentiate into steroid hormone-producing cells of three functionally distinct concentric zones that respond robustly to various endocrine stimuli. Wnt/β-catenin signaling mediates adrenocortical progenitor cell fate and tissue renewal to maintain the gland throughout life. Aberrant Wnt/β-catenin signaling contributes to various adrenal disorders of steroid production and growth that range from hypofunction and hypoplasia to hyperfunction, hyperplasia, benign adrenocortical adenomas, and malignant adrenocortical carcinomas. Great strides have been made in defining the molecular underpinnings of adrenocortical homeostasis and disease, including the interplay between the capsule and cortex, critical components involved in maintaining the adrenocortical Wnt/β-catenin signaling gradient, and new targets in adrenal cancer. This review seeks to examine these and other recent advancements in understanding adrenocortical Wnt/β-catenin signaling and how this knowledge can inform therapeutic options for adrenal disease.
Topics: Adrenal Cortex; Adrenal Gland Diseases; Animals; Humans; Ligands; Regeneration; Wnt Signaling Pathway; beta Catenin
PubMed: 33338548
DOI: 10.1016/j.mce.2020.111120 -
Reviews in Endocrine & Metabolic... Feb 2023The adrenal cortex undergoes multiple structural and functional rearrangements to satisfy the systemic needs for steroids during fetal life, postnatal development, and... (Review)
Review
The adrenal cortex undergoes multiple structural and functional rearrangements to satisfy the systemic needs for steroids during fetal life, postnatal development, and adulthood. A fully functional adrenal cortex relies on the proper subdivision in regions or 'zones' with distinct but interconnected functions, which evolve from the early embryonic stages to adulthood, and rely on a fine-tuned gene network. In particular, the steroidogenic activity of the fetal adrenal is instrumental in maintaining normal fetal development and growth. Here, we review and discuss the most recent advances in our understanding of embryonic and fetal adrenal development, including the known causes for adrenal dys-/agenesis, and the steroidogenic pathways that link the fetal adrenal with the hormone system of the mother through the fetal-placental unit. Finally, we discuss what we think are the major open questions in the field, including, among others, the impact of osteocalcin, thyroid hormone, and other hormone systems on adrenal development and function, and the reliability of rodents as models of adrenal pathophysiology.
Topics: Pregnancy; Female; Humans; Reproducibility of Results; Placenta; Adrenal Cortex; Adrenal Cortex Hormones
PubMed: 36255414
DOI: 10.1007/s11154-022-09756-3 -
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 -
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 -
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 -
Journal of Physiology and Pharmacology... Feb 2017Adrenocortical carcinoma is a rare disease with poor prognosis. Mitotane is the most effective agent in post-operative treatment (or when inoperable). It selectively... (Review)
Review
Adrenocortical carcinoma is a rare disease with poor prognosis. Mitotane is the most effective agent in post-operative treatment (or when inoperable). It selectively limits growth and bioactivity of adrenal tissue. Despite 60 years of use, the basis for its action has yet to be convincingly established. This review summarizes current knowledge of mitotane effects, based on studies on adrenal tissue and primary cell cultures, with emphasis on more recent studies of cell lines. We consider features of the adrenal cortex that might explain mitotane selectivity, and review effects on non-adrenal cells. Since the most clear-cut mitotane effects have been observed for mitochondria, this topic is the core of the review. Mitochondria present unique characteristics in steroidogenic tissue and are known to be important in malignancy development and apoptosis. We look at the evidence for mitotane activation within mitochondria, its impact on mitochondrial energy metabolism and other cellular processes as well as on downstream effects in the cell, such as apoptosis initiation. Further genomic and proteomic investigative studies are likely to yield useful results.
Topics: Adrenal Cortex; Adrenocortical Carcinoma; Animals; Antineoplastic Agents, Hormonal; Apoptosis; Cell Death; Humans; Mitochondria; Mitotane; Proteins; Proteome; Steroids
PubMed: 28456766
DOI: No ID Found -
International Journal of Molecular... May 2021Many adrenocortical diseases are more prevalent in women than in men, but the reasons underlying this sex bias are still unknown. Recent studies involving gonadectomy... (Review)
Review
Many adrenocortical diseases are more prevalent in women than in men, but the reasons underlying this sex bias are still unknown. Recent studies involving gonadectomy and sex hormone replacement experiments in mice have shed some light onto the molecular basis of sexual dimorphism in the adrenal cortex. Indeed, it has been shown that gonadal hormones influence many aspects of adrenal physiology, ranging from stem cell-dependent tissue turnover to steroidogenesis and X-zone dynamics. This article reviews current knowledge on adrenal cortex sexual dimorphism and the potential mechanisms underlying sex hormone influence of adrenal homeostasis. Both topics are expected to contribute to personalized and novel therapeutic approaches in the future.
Topics: Adrenal Cortex; Adrenal Gland Diseases; Animals; Female; Gonadal Steroid Hormones; Humans; Male; Sex Characteristics; Sexism; Signal Transduction
PubMed: 34063067
DOI: 10.3390/ijms22094889 -
Endocrinology and Metabolism (Seoul,... Dec 2020The adrenal gland plays a pivotal role in an organism's health span by controlling the endocrine system. Decades of research on the adrenal gland have provided... (Review)
Review
The adrenal gland plays a pivotal role in an organism's health span by controlling the endocrine system. Decades of research on the adrenal gland have provided multiscale insights into the development and maintenance of this essential organ. A particularly interesting finding is that founder stem/progenitor cells participate in adrenocortical development and enable the adult adrenal cortex to regenerate itself in response to hormonal stress and injury. Since major advances have been made in understanding the dynamics of the developmental process and the remarkable regenerative capacity of the adrenal gland, understanding the mechanisms underlying adrenal development, maintenance, and regeneration will be of interest to basic and clinical researchers. Here, we introduce the developmental processes of the adrenal gland and discuss current knowledge regarding stem/progenitor cells that regulate adrenal cortex remodeling and regeneration. This review will provide insights into the fascinating ongoing research on the development and regeneration of the adrenal cortex.
Topics: Adrenal Cortex; Adrenal Glands; Adult; Animals; Embryonic Development; Gene Expression Regulation, Developmental; Humans; Regeneration; Signal Transduction; Stem Cells
PubMed: 33397037
DOI: 10.3803/EnM.2020.403 -
Proceedings of the Japan Academy.... 2014The adrenal cortex of mammals consists of three concentric zones, i.e., the zona glomerulosa (zG), the zona fasciculata (zF), and the zona reticularis (zR), which... (Review)
Review
The adrenal cortex of mammals consists of three concentric zones, i.e., the zona glomerulosa (zG), the zona fasciculata (zF), and the zona reticularis (zR), which secrete mineralocorticoids, glucocorticoids, and adrenal androgens, respectively. In 1994, we identified immunohistochemically a new zone between zG and zF of the rat adrenal gland. The zone appeared to be devoid of any significant endocrine functions specific to adrenocortical zones, therefore, we designated the zone as "undifferentiated cell zone (zU)". Further, BrdU (5-bromo-2'-deoxyuridine)-incorporating cells (cells in S-phase) were concentrated at the outer region and the inner region of zU, and these cells proliferated and migrated bidirectionally: toward zG centrifugally and toward zF centripetally. We proposed that cells in and around zU are stem/progenitor cells of the rat adrenal cortex, maintaining functional zonation of the adrenal cortex. The view is consistent with observations reported recently that Sonic hedgehog (Shh), an important factor in embryonic development and adult stem cell maintenance, exists in zU of the rat adrenal gland and the Shh-containing cells seem to migrate bidirectionally.
Topics: Adrenal Cortex; Adrenal Cortex Hormones; Animals; Cell Differentiation; Humans; Rats; Steroids
PubMed: 24814991
DOI: 10.2183/pjab.90.163