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Adrenal zonation

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https://www.readbyqxmd.com/read/30029738/mutation-of-hsd3b2-gene-and-fate-of-dehydroepiandrosterone
#1
Maria Sonia Baquedano, Gabriela Guercio, Mariana Costanzo, Roxana Marino, Marco A Rivarola, Alicia Belgorosky
3βHSD2 enzyme is crucial for adrenal and gonad steroid biosynthesis. In enzyme deficiency states, due to recessive loss-of-function HSD3B2 mutations, steroid flux is altered and clinical manifestations result. Deficiency of 3βHSD2 activity in the adrenals precludes normal aldosterone and cortisol synthesis and the alternative backdoor and 11-oxygenated C19 steroid pathways and the flooding of cortisol precursors along the Δ5 pathway with a marked rise in DHEA and DHEAS production. In gonads, it precludes normal T and estrogen synthesis...
2018: Vitamins and Hormones
https://www.readbyqxmd.com/read/30007283/the-biology-of-normal-zona-glomerulosa-and-aldosterone-producing-adenoma-pathological-implications
#2
Teresa M Seccia, Brasilina Caroccia, Elise P Gomez-Sanchez, Celso E Gomez-Sanchez, Gian Paolo Rossi
The identification of several germline and somatic ion channel mutations in aldosterone-producing adenomas (APA) and detection of cell clusters that can be responsible for excess aldosterone production, as well as the isolation of autoantibodies activating the angiotensin II type 1 receptor, have rapidly advanced the understanding of the biology of primary aldosteronism (PA), in particular that of APA. Hence, the main purpose of this review is to discuss how discoveries of the last decade could impact on histopathology analysis and clinical practice...
July 10, 2018: Endocrine Reviews
https://www.readbyqxmd.com/read/29879378/mrap-deficiency-impairs-adrenal-progenitor-cell-differentiation-and-gland-zonation
#3
Tatiana V Novoselova, Mashal Hussain, Peter J King, Leonardo Guasti, Louise A Metherell, Marika Charalambous, Adrian J L Clark, Li F Chan
Melanocortin 2 receptor accessory protein (MRAP) is a single transmembrane domain accessory protein and a critical component of the hypothamo-pituitary-adrenal axis. MRAP is highly expressed in the adrenal gland and is essential for adrenocorticotropin hormone (ACTH) receptor expression and function. Human loss-of-function mutations in MRAP cause familial glucocorticoid (GC) deficiency (FGD) type 2 (FGD2), whereby the adrenal gland fails to respond to ACTH and to produce cortisol. In this study, we generated Mrap-null mice to study the function of MRAP in vivo...
June 7, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29742513/human-adrenal-cortex-epigenetics-and-postnatal-functional-zonation
#4
María Sonia Baquedano, Alicia Belgorosky
The human adrenal cortex, involved in adaptive responses to stress, fluid homeostasis, and secondary sexual characteristics, arises from a tightly regulated development of a zone and cell type-specific secretory pattern. However, the molecular mechanisms governing adrenal zonation, particularly postnatal zona reticularis development, which produce adrenal androgens in a lifetime-specific manner, remain poorly understood. Epigenetic events, including DNA and histone modifications as well as regulation by noncoding RNAs, are crucial in establishing or maintaining the expression pattern of specific genes and thus contribute to the stability of a specific differentiation state...
2018: Hormone Research in Pædiatrics
https://www.readbyqxmd.com/read/29212953/the-e3-ubiquitin-ligase-siah1-regulates-adrenal-gland-organization-and-aldosterone-secretion
#5
Marzia Scortegagna, Annabel Berthon, Nikolaos Settas, Andreas Giannakou, Guillermina Garcia, Jian-Liang Li, Brian James, Robert C Liddington, José G Vilches-Moure, Constantine A Stratakis, Ze'ev A Ronai
Primary and secondary hypertension are major risk factors for cardiovascular disease, the leading cause of death worldwide. Elevated secretion of aldosterone resulting from primary aldosteronism (PA) is a key driver of secondary hypertension. Here, we report an unexpected role for the ubiquitin ligase Siah1 in adrenal gland development and PA. Siah1a-/- mice exhibit altered adrenal gland morphology, as reflected by a diminished X-zone, enlarged medulla, and dysregulated zonation of the glomerulosa as well as increased aldosterone levels and aldosterone target gene expression and reduced plasma potassium levels...
December 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/27793677/disordered-zonal-and-cellular-cyp11b2-enzyme-expression-in-familial-hyperaldosteronism-type-3
#6
Celso E Gomez-Sanchez, Xin Qi, Elise P Gomez-Sanchez, Hironobu Sasano, Martin O Bohlen, Max Wisgerhof
Three forms of familial primary aldosteronism have been recognized. Familial Hyperaldosteronism type 1 (FH1) or dexamethasone suppressible hyperaldosteronism, FH2, the most common form of as yet unknown cause(s), and FH3. FH3 is due to activating mutations of the potassium channel gene KCNJ5 that increase constitutive and angiotensin II-induced aldosterone synthesis. In this study we examined the cellular distribution of CYP11B2, CYP11B1, CYP17A1 and KCNJ5 in adrenals from two FH3 siblings using immunohistochemistry and immunofluorescence and obtained unexpected results...
January 5, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27751767/immunohistochemistry-of-aldosterone-synthase-leads-the-way-to-the-pathogenesis-of-primary-aldosteronism
#7
REVIEW
Koshiro Nishimoto, Minae Koga, Tsugio Seki, Kenji Oki, Elise P Gomez-Sanchez, Celso E Gomez-Sanchez, Mitsuhide Naruse, Tomokazu Sakaguchi, Shinya Morita, Takeo Kosaka, Mototsugu Oya, Tadashi Ogishima, Masanori Yasuda, Makoto Suematsu, Yasuaki Kabe, Masao Omura, Tetsuo Nishikawa, Kuniaki Mukai
Our group previously purified human and rat aldosterone synthase (CYP11B2 and Cyp11b2, respectively) from their adrenals and verified that it is distinct from steroid 11β-hydroxylase (CYP11B1 or Cyp11b1), the cortisol- or corticosterone-synthesizing enzyme. We now describe their distributions immunohistochemically with specific antibodies. In rats, there is layered functional zonation with the Cyp11b2-positive zona glomerulosa (ZG), Cyp11b1-positive zona fasciculata (ZF), and Cyp11b2/Cyp11b1-negative undifferentiated zone between the ZG and ZF...
February 5, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27721827/human-adrenocortical-remodeling-leading-to-aldosterone-producing-cell-cluster-generation
#8
Koshiro Nishimoto, Tsugio Seki, Yuichiro Hayashi, Shuji Mikami, Ghaith Al-Eyd, Ken Nakagawa, Shinya Morita, Takeo Kosaka, Mototsugu Oya, Fumiko Mitani, Makoto Suematsu, Yasuaki Kabe, Kuniaki Mukai
Background. The immunohistochemical detection of aldosterone synthase (CYP11B2) and steroid 11β-hydroxylase (CYP11B1) has enabled the identification of aldosterone-producing cell clusters (APCCs) in the subcapsular portion of the human adult adrenal cortex. We hypothesized that adrenals have layered zonation in early postnatal stages and are remodeled to possess APCCs over time. Purposes. To investigate changes in human adrenocortical zonation with age. Methods. We retrospectively analyzed adrenal tissues prepared from 33 autopsied patients aged between 0 and 50 years...
2016: International Journal of Endocrinology
https://www.readbyqxmd.com/read/27670690/dna-methylation-is-not-involved-in-specific-down-regulation-of-hsd3b2-nr4a1-and-rarb-genes-in-androgen-secreting-cells-of-human-adrenal-cortex
#9
María Sonia Baquedano, Natalia Perez Garrido, Javier Goñi, Nora Saraco, Paula Aliberti, Esperanza Berensztein, Marco A Rivarola, Alicia Belgorosky
We hypothesized that DNA methylation is involved in human adrenal functional zonation. mRNAs expression and methylation pattern of RARB, NR4A1 and HSD3B2 genes in human adrenal tissues (HAT) and in pediatric virilizing adrenocortical tumors (VAT) were analyzed. For analysis of the results samples were divided into 3 age groups according to FeZ involution, pre and post-adrenarche ages. In all HAT, similar RARB mRNA was found including microdissected zona reticularis (ZR) and zona fasciculata, but HSD3B2 and NR4A1 mRNAs were lower in ZR (p < 0...
February 5, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27624192/pka-inhibits-wnt-signalling-in-adrenal-cortex-zonation-and-prevents-malignant-tumour-development
#10
Coralie Drelon, Annabel Berthon, Isabelle Sahut-Barnola, Mickaël Mathieu, Typhanie Dumontet, Stéphanie Rodriguez, Marie Batisse-Lignier, Houda Tabbal, Igor Tauveron, Anne-Marie Lefrançois-Martinez, Jean-Christophe Pointud, Celso E Gomez-Sanchez, Seppo Vainio, Jingdong Shan, Sonia Sacco, Andreas Schedl, Constantine A Stratakis, Antoine Martinez, Pierre Val
Adrenal cortex physiology relies on functional zonation, essential for production of aldosterone by outer zona glomerulosa (ZG) and glucocorticoids by inner zona fasciculata (ZF). The cortex undergoes constant cell renewal, involving recruitment of subcapsular progenitors to ZG fate and subsequent lineage conversion to ZF identity. Here we show that WNT4 is an important driver of WNT pathway activation and subsequent ZG differentiation and demonstrate that PKA activation prevents ZG differentiation through WNT4 repression and WNT pathway inhibition...
September 14, 2016: Nature Communications
https://www.readbyqxmd.com/read/27619404/regulation-of-zonation-and-homeostasis-in-the-adrenal-cortex
#11
REVIEW
Emanuele Pignatti, Sining Leng, Diana L Carlone, David T Breault
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...
February 5, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27524977/adrenal-mitochondria-and-steroidogenesis-from-individual-proteins-to-functional-protein-assemblies
#12
REVIEW
Andrew Midzak, Vassilios Papadopoulos
The adrenal cortex is critical for physiological function as the central site of glucocorticoid and mineralocorticoid synthesis. It possesses a great degree of specialized compartmentalization at multiple hierarchical levels, ranging from the tissue down to the molecular levels. In this paper, we discuss this functionalization, beginning with the tissue zonation of the adrenal cortex and how this impacts steroidogenic output. We then discuss the cellular biology of steroidogenesis, placing special emphasis on the mitochondria...
2016: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/27378832/functional-zonation-of-the-adult-mammalian-adrenal-cortex
#13
REVIEW
Gavin P Vinson
The standard model of adrenocortical zonation holds that the three main zones, glomerulosa, fasciculata, and reticularis each have a distinct function, producing mineralocorticoids (in fact just aldosterone), glucocorticoids, and androgens respectively. Moreover, each zone has its specific mechanism of regulation, though ACTH has actions throughout. Finally, the cells of the cortex originate from a stem cell population in the outer cortex or capsule, and migrate centripetally, changing their phenotype as they progress through the zones...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27313319/the-adrenal-capsule-is-a-signaling-center-controlling-cell-renewal-and-zonation-through-rspo3
#14
Valerie Vidal, Sonia Sacco, Ana Sofia Rocha, Fabio da Silva, Clara Panzolini, Typhanie Dumontet, Thi Mai Phuong Doan, Jingdong Shan, Aleksandra Rak-Raszewska, Tom Bird, Seppo Vainio, Antoine Martinez, Andreas Schedl
Adrenal glands are zonated endocrine organs that are essential in controlling body homeostasis. How zonation is induced and maintained and how renewal of the adrenal cortex is ensured remain a mystery. Here we show that capsular RSPO3 signals to the underlying steroidogenic compartment to induce β-catenin signaling and imprint glomerulosa cell fate. Deletion of RSPO3 leads to loss of SHH signaling and impaired organ growth. Importantly, Rspo3 function remains essential in adult life to ensure replenishment of lost cells and maintain the properties of the zona glomerulosa...
June 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/27108660/new-insights-in-the-functional-zonation-of-the-canine-adrenal-cortex
#15
K Sanders, J A Mol, H S Kooistra, A Slob, S Galac
BACKGROUND: Current understanding of adrenal steroidogenesis is that the production of aldosterone or cortisol depends on the expression of aldosterone synthase (CYP11B2) and 11β-hydroxylase cytochrome P450 (CYP11B1), respectively. However, this has never been studied in dogs, and in some species, a single CYP11B catalyzes both cortisol and aldosterone formation. Analysis of the canine genome provides data of a single CYP11B gene which is called CYP11B2, and a large sequence gap exists near the so-called CYP11B2 gene...
May 2016: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/26141512/fgfr2-is-required-for-the-expansion-of-the-early-adrenocortical-primordium
#16
Regine Häfner, Tobias Bohnenpoll, Carsten Rudat, Thomas M Schultheiss, Andreas Kispert
The adrenal cortex is a critical steroidogenic endocrine tissue, generated at least in part from intermediate mesoderm of the anterior urogenital ridge. Previous work has pinpointed a minor role of the FGFR2IIIb isoform in expansion and differentiation of the fetal adrenal cortex in mice but did not address the complete role of FGFR2 and FGFR1 signaling in adrenocortical development. Here, we show that a Tbx18(cre) line mediates specific recombination in the coelomic epithelium of the anterior urogenital ridge which gives rise by a delamination process to the adrenocortical primordium...
September 15, 2015: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/26038200/development-of-adrenal-cortex-zonation
#17
REVIEW
Yewei Xing, Antonio M Lerario, William Rainey, Gary D Hammer
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...
June 2015: Endocrinology and Metabolism Clinics of North America
https://www.readbyqxmd.com/read/25798129/adrenocortical-zonation-renewal-and-remodeling
#18
REVIEW
Marjut Pihlajoki, Julia Dörner, Rebecca S Cochran, Markku Heikinheimo, David B Wilson
The adrenal cortex is divided into concentric zones. In humans the major cortical zones are the zona glomerulosa, zona fasciculata, and zona reticularis. The adrenal cortex is a dynamic organ in which senescent cells are replaced by newly differentiated ones. This constant renewal facilitates organ remodeling in response to physiological demand for steroids. Cortical zones can reversibly expand, contract, or alter their biochemical profiles to accommodate needs. Pools of stem/progenitor cells in the adrenal capsule, subcapsular region, and juxtamedullary region can differentiate to repopulate or expand zones...
2015: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/25589272/adrenocortical-growth-and-cancer
#19
REVIEW
Lucile Lefèvre, Jérôme Bertherat, Bruno Ragazzon
The adrenal gland consists of two distinct parts, the cortex and the medulla. Molecular mechanisms controlling differentiation and growth of the adrenal gland have been studied in detail using mouse models. Knowledge also came from investigations of genetic disorders altering adrenal development and/or function. During embryonic development, the adrenal cortex acquires a structural and functional zonation in which the adrenal cortex is divided into three different steroidogenic zones. Significant progress has been made in understanding adrenal zonation...
January 2015: Comprehensive Physiology
https://www.readbyqxmd.com/read/25542843/adrenal-cortex-tissue-homeostasis-and-zonation-a-wnt-perspective
#20
REVIEW
Coralie Drelon, Annabel Berthon, Mickael Mathieu, Antoine Martinez, Pierre Val
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...
June 15, 2015: Molecular and Cellular Endocrinology
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