Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (837 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
The outer layer of the adrenal gland. It is derived from mesoderm and comprised of three zones (outer zona glomerulosa, middle zona fasciculata, and inner zona reticularis) with each producing various steroids preferentially, such as aldosterone; hydrocortisone; dehydroepiandrosterone; and androstenedione. Adrenal cortex function is regulated by pituitary adrenocorticotropin.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Cortex, Adrenal.
Where it fits in the MeSH classification
- Broader topics
- Adrenal Glands
- Narrower topics
- Zona Fasciculata; Zona Glomerulosa; Zona Reticularis
Related concepts
- Mesoderm
- Zona Glomerulosa
- Zona Fasciculata
- Zona Reticularis
- Aldosterone
- Hydrocortisone
- Dehydroepiandrosterone
- Androstenedione
- Adrenocorticotropic Hormone
Research landscape
PubMed indexes 19,546 records tagged with the MeSH heading “Adrenal Cortex” (counts retrieved 2026-10-31). 326 of them (1.7%) were published from 2020 onward, and the busiest period so far is through 1999 with 16,594 records.
Reviews account for 1,034 records (5.3%) and meta-analyses for 6. Randomized controlled trials number 69 (0.4%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 16,594 |
| 2000-2009 | 1,664 |
| 2010-2019 | 962 |
| 2020 onward | 326 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 1,034 | 5.3% |
| Meta-analyses | 6 | 0.0% |
| Randomized controlled trials | 69 | 0.4% |
Method: PubMed query "Adrenal Cortex"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in anatomy and physiology
Anatomy describes how body structures are built and physiology describes how they normally work, so most findings here are descriptive or mechanistic rather than evidence about treatment. Much of what is known comes from dissection, imaging, tissue studies and experiments in animals, and measurements in healthy volunteers can differ from those in people with disease or at different ages. Normal ranges vary between individuals and populations. Check whether a result was measured in people or in another species, the age and health of the participants, and the method used.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| PKA inhibits WNT signalling in adrenal cortex zonation and prevents malignant tumour development | 2016 | Research article Design not recorded in structured metadata | 101 | cc by PMID 27624192 · DOI · PMC5027289 |
| The Adrenal Cortex, an Underestimated Site of SARS-CoV-2 Infection | 2020 | Research article Design not recorded in structured metadata | 69 | cc by PMID 33488517 · DOI · PMC7820749 |
| Active steroid hormone synthesis renders adrenocortical cells highly susceptible to type II ferroptosis induction | 2020 | Research article Design not recorded in structured metadata | 63 | cc by PMID 32184394 · DOI · PMC7078189 |
| Rho/ROCK signaling and α-catenin mediate β-catenin-driven hyperplasia in the adrenal cortex via adherens junctions | 2026 | Research article Design not recorded in structured metadata | 2 | cc by PMID 41591811 · DOI · PMC12987613 |
PKA inhibits WNT signalling in adrenal cortex zonation and prevents malignant tumour development [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Adrenal cortex physiology relies on functional zonation, essential for production of aldosterone by outer zona glomerulosa (ZG) and glucocorticoids by inner zona fasciculata (ZF).
- Closing excerpt
- These observations suggest that PKA acts as a tumour suppressor in the adrenal cortex, through repression of WNT signalling.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (151 words)
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. This suggests that PKA activation in ZF is a key driver of WNT inhibition and lineage conversion. Furthermore, we provide evidence that constitutive PKA activation inhibits, whereas partial inactivation of PKA catalytic activity stimulates β-catenin-induced tumorigenesis. Together, both lower PKA activity and higher WNT pathway activity lead to poorer prognosis in adrenocortical carcinoma (ACC) patients. These observations suggest that PKA acts as a tumour suppressor in the adrenal cortex, through repression of WNT signalling.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 27624192 · DOI · PMC5027289
The Adrenal Cortex, an Underestimated Site of SARS-CoV-2 Infection [2]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundThe majority of the critically ill patients may have critical illness-related corticosteroid insufficiency (CIRCI).
- Closing excerpt
- Based on our findings, we recommend measuring plasma cortisol level to guide hormonal therapy.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (240 words)
BackgroundThe majority of the critically ill patients may have critical illness-related corticosteroid insufficiency (CIRCI). The therapeutic effect of dexamethasone may be related to its ability to improve cortical function. Recent study showed that dexamethasone can reduce COVID-19 deaths by up to one third in critically ill patients. The aim of this article is to investigate whether SARS-CoV-2 can attack the adrenal cortex to aggravate the relative adrenal insufficiency.MethodsWe summarized the clinical features of COVID-19 reported in currently available observational studies. ACE2 and TMPRSS2 expression was examined in human adrenal glands by immunohistochemical staining. We retrospectively analyzed serum cortisol levels in critically ill patients with or without COVID-19.ResultsHigh percentage of critically ill patients with SARS-COV-2 infection in the study were treated with vasopressors. ACE2 receptor and TMPRSS2 serine protease were colocalized in adrenocortical cells in zona fasciculata and zona reticularis. We collected plasma cortisol concentrations in nine critically ill patients with COVID-19. The cortisol levels of critically ill patients with COVID-19 were lower than those in non-COVID-19 critically ill group. Six of the nine COVID-19 critically ill patients had random plasma cortisol concentrations below 10 µg/dl, which met the criteria for the diagnosis of CIRCI.ConclusionWe demonstrate that ACE2 and TMPRSS2 are colocalized in adrenocortical cells, and that the cortisol levels are lower in critically ill patients with COVID-19 as compared to those of non-COVID-19 critically ill patients. Based on our findings, we recommend measuring plasma cortisol level to guide hormonal therapy.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 33488517 · DOI · PMC7820749
Active steroid hormone synthesis renders adrenocortical cells highly susceptible to type II ferroptosis induction [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Conditions of impaired adrenal function and tissue destruction, such as in Addison's disease, and treatment resistance of adrenocortical carcinoma (ACC) necessitate improved understanding of the pathophysiology of adrenal cell death.
- Closing excerpt
- Mitotane does not induce this form of cell death in ACC cells.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (243 words)
Conditions of impaired adrenal function and tissue destruction, such as in Addison's disease, and treatment resistance of adrenocortical carcinoma (ACC) necessitate improved understanding of the pathophysiology of adrenal cell death. Due to relevant oxidative processes in the adrenal cortex, our study investigated the role of ferroptosis, an iron-dependent cell death mechanism and found high adrenocortical expression of glutathione peroxidase 4 (GPX4) and long-chain-fatty-acid CoA ligase 4 (ACSL4) genes, key factors in the initiation of ferroptosis. By applying MALDI mass spectrometry imaging to normal and neoplastic adrenocortical tissue, we detected high abundance of arachidonic and adrenic acid, two long chain polyunsaturated fatty acids which undergo peroxidation during ferroptosis. In three available adrenal cortex cell models (H295R, CU-ACC1 and CU-ACC-2) a high susceptibility to GPX4 inhibition with RSL3 was documented with EC50 values of 5.7 × 10-8, 8.1 × 10-7 and 2.1 × 10-8 M, respectively, while all non-steroidogenic cells were significantly less sensitive. Complete block of GPX4 activity by RSL3 led to ferroptosis which was completely reversed in adrenal cortex cells by inhibition of steroidogenesis with ketoconazole but not by blocking the final step of cortisol synthesis with metyrapone. Mitotane, the only approved drug for ACC did not induce ferroptosis, despite strong induction of lipid peroxidation in ACC cells. Together, this report is the first to demonstrate extraordinary sensitivity of adrenal cortex cells to ferroptosis dependent on their active steroid synthetic pathways. Mitotane does not induce this form of cell death in ACC cells.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 32184394 · DOI · PMC7078189
Rho/ROCK signaling and α-catenin mediate β-catenin-driven hyperplasia in the adrenal cortex via adherens junctions [4]
Abstract reading summary — source excerpts
- Opening excerpt
- How β-catenin (βCat) mediates tissue hyperplasia is poorly understood.
- Closing excerpt
- Together, our findings identified Rho/ROCK signaling and αCat as key mediators of AJ formation and βCat-driven hyperplasia.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (203 words)
How β-catenin (βCat) mediates tissue hyperplasia is poorly understood. To explore this, we employed the adrenal cortex as a model system given its stereotypical spatial organization and the important role βCat plays in homeostasis and disease. For example, excessive production of aldosterone by the adrenal cortex (primary aldosteronism [PA]) is a major cause of cardiovascular morbidity and is associated with βCat gain of function (βCat-GOF). Adherens junctions (AJs) connect the actin cytoskeletons of adjacent zona glomerulosa (zG) cells via a cadherin-βCat-α-catenin complex and mediate aldosterone production. Whether βCat-GOF drives zG hyperplasia, a key feature of PA, via AJs is unknown. Here, we showed that aldosterone secretagogues (K+ and AngII) and βCat-GOF mediated AJ formation via Rho/ROCK/actomyosin signaling. In addition, Rho/ROCK inhibition led to altered zG rosette morphology and decreased aldosterone production. Mice with zG-specific βCat-GOF demonstrated increased AJ formation and zG hyperplasia, which was blunted by Rho/ROCK inhibition and deletion of α-catenin (αCat). βCat also impacted AJ formation independently of its role as a transcription factor. Furthermore, analysis of human aldosterone-producing adenomas revealed high levels of βCat expression were associated with increased membranous expression of K-cadherin. Together, our findings identified Rho/ROCK signaling and αCat as key mediators of AJ formation and βCat-driven hyperplasia.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41591811 · DOI · PMC12987613
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Developmental and functional biology of the primate fetal adrenal cortex [5]
- Research article Regulation of the synthesis of steroidogenic enzymes in adrenal cortical cells by ACTH [6]
- Research article Maturation of the adrenocortical stress response: neuroendocrine control mechanisms and the stress hyporesponsive period [7]
- Research article Consensus statement on the diagnosis, treatment and follow-up of patients with primary adrenal insufficiency [8]
- Research article The effects of neonatal handling on the development of the adrenocortical response to stress: implications for neuropathology and cognitive deficits in later life [9]
- Research article Clinical review 104: Adrenocorticotropin (ACTH)- and non-ACTH-mediated regulation of the adrenal cortex: neural and immune inputs [10]
References
- Drelon C, Berthon A, Sahut-Barnola I, Mathieu M, Dumontet T, Rodriguez S, et al.. PKA inhibits WNT signalling in adrenal cortex zonation and prevents malignant tumour development. . 2016. PMID 27624192 · DOI · PMC5027289
- Mao Y, Xu B, Guan W, Xu D, Li F, Ren R, et al.. The Adrenal Cortex, an Underestimated Site of SARS-CoV-2 Infection. . 2020. PMID 33488517 · DOI · PMC7820749
- Weigand I, Schreiner J, Röhrig F, Sun N, Landwehr LS, Urlaub H, et al.. Active steroid hormone synthesis renders adrenocortical cells highly susceptible to type II ferroptosis induction. . 2020. PMID 32184394 · DOI · PMC7078189
- Berber M, Haykir B, Guagliardo NA, Chortis V, Borges KS, Barrett PQ, et al.. Rho/ROCK signaling and α-catenin mediate β-catenin-driven hyperplasia in the adrenal cortex via adherens junctions. . 2026. PMID 41591811 · DOI · PMC12987613
- Mesiano S, Jaffe RB. Developmental and functional biology of the primate fetal adrenal cortex. Endocr Rev. 1997. PMID 9183569 · DOI
- Simpson ER, Waterman MR. Regulation of the synthesis of steroidogenic enzymes in adrenal cortical cells by ACTH. Annu Rev Physiol. 1988. PMID 2837136 · DOI
- Sapolsky RM, Meaney MJ. Maturation of the adrenocortical stress response: neuroendocrine control mechanisms and the stress hyporesponsive period. Brain Res. 1986. PMID 3011218 · DOI
- Husebye ES, Allolio B, Arlt W, Badenhoop K, Bensing S, Betterle C, et al.. Consensus statement on the diagnosis, treatment and follow-up of patients with primary adrenal insufficiency. J Intern Med. 2014. PMID 24330030 · DOI
- Meaney MJ, Mitchell JB, Aitken DH, Bhatnagar S, Bodnoff SR, Iny LJ, et al.. The effects of neonatal handling on the development of the adrenocortical response to stress: implications for neuropathology and cognitive deficits in later life. Psychoneuroendocrinology. 1991. PMID 1961847 · DOI
- Bornstein SR, Chrousos GP. Clinical review 104: Adrenocorticotropin (ACTH)- and non-ACTH-mediated regulation of the adrenal cortex: neural and immune inputs. J Clin Endocrinol Metab. 1999. PMID 10323408 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.