Adrenal cortex renewal in health and disease

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.

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.

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.).

Université Côte d’Azur, INSERM, CNRS, Institut de Biologie Valrose, Nice, France

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.

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.

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