Journal
JCI INSIGHT
Volume 3, Issue 2, Pages -Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.98394
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Funding
- CNRS
- INSERM
- Universite Clermont Auvergne
- French government IDEX-ISITE initiative [16-IDEX-0001 (CAP 20-25)]
- Region Auvergne-Rhone-Alpes
- Fondation Association pour la Recherche sur le Cancer
- Agence Nationale pour la Recherche [ANR-14-CE12-000]
- NIH [R01 DK 084056]
- Grants-in-Aid for Scientific Research [17H06427, 16H05142] Funding Source: KAKEN
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The adrenal cortex undergoes remodeling during fetal and postnatal life. How zona reticularis emerges in the postnatal gland to support adrenarche, a process whereby higher primates increase prepubertal androgen secretion, is unknown. Using cell-fate mapping and gene deletion studies in mice, we show that activation of PKA has no effect on the fetal cortex, while it accelerates regeneration of the adult cortex, triggers zona fasciculata differentiation that is subsequently converted into a functional reticularis-like zone, and drives hypersecretion syndromes. Remarkably, PKA effects are influenced by sex. Indeed, testicular androgens increase WNT signaling that antagonizes PKA, leading to slower adrenocortical cell turnover and delayed phenotype whereas gonadectomy sensitizes males to hypercorticism and reticularis-like formation. Thus, reticularis results from ultimate centripetal conversion of adult cortex under the combined effects of PKA and cell turnover that dictate organ size. We show that PKA-induced progenitor recruitment is sexually dimorphic and may provide a paradigm for overrepresentation of women in adrenal diseases.
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