ArticlePLoS genetics2010
Cushing's syndrome and fetal features resurgence in adrenal cortex-specific Prkar1a knockout mice.
Article in PLoS genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
58 citing papers in PubMed, 111 citations in OpenAlex.
- Does somatostatin have a role in the regulation of cortisol secretion in primary pigmented nodular adrenocortical disease (ppnad)? a clinical and in vitro investigation.The Journal of clinical endocrinology and metabolism · 2014Trial
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- Adrenal lipoma formation via PI(3,4,5)PProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Sexual dimorphism in benign adrenocortical tumours.European journal of endocrinology · 2025Review
- Current insight into the transient X-zone in the adrenal gland cortex.Vitamins and hormones · 2024Review
- Restricted effects of androgens on glucocorticoid signaling in the mouse prefrontal cortex and midbrain.Frontiers in endocrinology · 2023Article
- Loss of SUMO-specific protease 2 causes isolated glucocorticoid deficiency by blocking adrenal cortex zonal transdifferentiation in mice.Nature communications · 2022Article
- Update on Biology and Genomics of Adrenocortical Carcinomas: Rationale for Emerging Therapies.Endocrine reviews · 2022Article
- Transgenic Mouse Models to Study the Development and Maintenance of the Adrenal Cortex.International journal of molecular sciences · 2022Review
- Effect of Inactivation ofJournal of the Endocrine Society · 2022Article
- Treatment of Primary Pigmented Nodular Adrenocortical Disease.Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme · 2022Review
- Genetic Alterations in Benign Adrenal Tumors.Biomedicines · 2022Review
- Gene expression changes in the brain of a Cushing's syndrome mouse model.Journal of neuroendocrinology · 2022Article
- Bones and adrenal organogenesis: how embryonic osteocalcin influences lifelong adrenal function.The Journal of clinical investigation · 2022Article
- The cAMP-signaling cancers: Clinically-divergent disorders with a common central pathway.Frontiers in endocrinology · 2022Review
- Protein kinase A drives paracrine crisis and WNT4-dependent testis tumor in Carney complex.The Journal of clinical investigation · 2021Article
- Bilateral Adrenal Hyperplasia: Pathogenesis and Treatment.Biomedicines · 2021Review
- Adrenal cortex renewal in health and disease.Nature reviews. Endocrinology · 2021Review
- Cushing Syndrome in a Pediatric Patient With a KCNJ5 Variant and Successful Treatment With Low-dose Ketoconazole.The Journal of clinical endocrinology and metabolism · 2021Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
Carney complex (CNC) is an inherited neoplasia syndrome with endocrine overactivity. Its most frequent endocrine manifestation is primary pigmented nodular adrenocortical disease (PPNAD), a bilateral adrenocortical hyperplasia causing pituitary-independent Cushing's syndrome. Inactivating mutations in PRKAR1A, a gene encoding the type 1 alpha-regulatory subunit (R1alpha) of the cAMP-dependent protein kinase (PKA) have been found in 80% of CNC patients with Cushing's syndrome. To demonstrate the implication of R1alpha loss in the initiation and development of PPNAD, we generated mice lacking Prkar1a specifically in the adrenal cortex (AdKO). AdKO mice develop pituitary-independent Cushing's syndrome with increased PKA activity. This leads to autonomous steroidogenic genes expression and deregulated adreno-cortical cells differentiation, increased proliferation and resistance to apoptosis. Unexpectedly, R1alpha loss results in improper maintenance and centrifugal expansion of cortisol-producing fetal adrenocortical cells with concomitant regression of adult cortex. Our data provide the first in vivo evidence that loss of R1alpha is sufficient to induce autonomous adrenal hyper-activity and bilateral hyperplasia, both observed in human PPNAD. Furthermore, this model demonstrates that deregulated PKA activity favors the emergence of a new cell population potentially arising from the fetal adrenal, giving new insight into the mechanisms leading to PPNAD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.