Adrenal cortex renewal in health and disease

ABSTRACT 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. KEY POINTS * The adrenal cortex undergoes renewal throughout life and can

regenerate after injury thanks to resident progenitor populations. * Paracrine and endocrine mechanisms regulate progenitor cell activity and establish adrenal cortex zonation; disruption of

these mechanisms leads to alterations in adrenal size. * Adrenocortical tissue turnover is sexually dimorphic owing, at least in part, to a suppressive effect of testicular androgens. *

Dysregulation of adrenocortical turnover pathways is associated with development of adrenal tumours. Access through your institution Buy or subscribe This is a preview of subscription

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* Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS ADRENOCORTICAL STEM CELLS IN HEALTH AND DISEASE Article 10 March

2025 SOX2+ SUSTENTACULAR CELLS ARE STEM CELLS OF THE POSTNATAL ADRENAL MEDULLA Article Open access 02 January 2025 AGING INDUCES REGION-SPECIFIC DYSREGULATION OF HORMONE SYNTHESIS IN THE

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reducing aldosterone production. _Endocrinology_ 143, 4358–4365 (2002). Article  PubMed  Google Scholar  Download references ACKNOWLEDGEMENTS The authors thank C. Stratakis for his input and

for critically reading this manuscript. The authors’ research work is supported by La Ligue Contre le Cancer (Equipe Labellisée to A.S.), Agence Nationale de la Recherche

(ANR-11-LABX-0028-01 to A.S. and ANR-18-CE14-0012), World Wide Cancer Research (WWCR) (18-0437 to A.S.), International Fund for Congenital Adrenal Hyperpalsia (IFCAH 2017 to A.S.) and

Fondation pour la Recherche Médicale (FRM SPF201809007141 to R.L.). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Université Côte d’Azur, INSERM, CNRS, Institut de Biologie Valrose, Nice,

France Rodanthi Lyraki & Andreas Schedl Authors * Rodanthi Lyraki View author publications You can also search for this author inPubMed Google Scholar * Andreas Schedl View author

publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS A.S. and R.L. researched data for the article, contributed to discussions of its content, wrote the

manuscript, and participated in review or editing of the manuscript before submission. CORRESPONDING AUTHOR Correspondence to Andreas Schedl. ETHICS DECLARATIONS COMPETING INTERESTS The

authors declare no competing interests. ADDITIONAL INFORMATION PEER REVIEW INFORMATION _Nature Reviews Endocrinology_ thanks J. Bertherat, who co-reviewed with I. Cavalcante, F. Beuschlein,

and S. Bornstein for their contribution to the peer review of this work. PUBLISHER’S NOTE Springer Nature remains neutral with regard to jurisdictional claims in published maps and

institutional affiliations. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Lyraki, R., Schedl, A. Adrenal cortex renewal in health and disease. _Nat Rev

Endocrinol_ 17, 421–434 (2021). https://doi.org/10.1038/s41574-021-00491-4 Download citation * Accepted: 30 March 2021 * Published: 19 May 2021 * Issue Date: July 2021 * DOI:

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