Adrenal rather than central dysfunction limits HPA axis recovery after chronic glucocorticoid treatment in male mice
Clics: 27
ID: 321443
2026
Metricas de Calidad y Rendimiento del Articulo
Calidad General
Not rated
Combines reader engagement with the AI quality analysis. This
article has not been analysed, so there is no overall score —
reader engagement is measured and shown alongside.
Participacion del Lector
Emerging Content
7.8
/100
27 vistas
8 lectores
Evaluacion de Calidad por IA
No analizado
Readership in this journal
EmergingRanked #187 of 308 articles by views in american journal of physiology endocrinology and metabolism
Most read
Least read
Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 308 in total.
Mint this article as an NFT
Not yet mintedCreate a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.
5
SUSD
one-off · no wallet required
Resumen
Glucocorticoid-induced adrenal insufficiency (GIAI) can persist for months after discontinuation of chronic corticosteroid therapy, placing patients at risk for life-threatening adrenal crises. This prolonged suppression has been attributed primarily to delayed restoration of hypothalamic-pituitary signaling based on indirect measures of central axis activity. To identify the rate-limiting site of hypothalamic-pituitary-adrenal (HPA) axis recovery, we evaluated the timing of functional and histologic recovery at each node of the axis following 8 weeks of dexamethasone (DEX) treatment in adult, male mice. DEX administration fully suppressed HPA axis activity. Unexpectedly, within one week of DEX withdrawal, hypothalamic Crh mRNA and plasma ACTH rebounded above control levels, whereas corticosterone (CORT) remained suppressed for an additional seven weeks. DEX-treated adrenals were markedly atrophic and contained large clusters of lipid-filled macrophages. Even after adjusting for macrophage content, CORT secretion was disproportionately low relative to the remaining adrenocortical cell mass despite supraphysiologic ACTH stimulation. The adrenal is thus the principal site of post-withdrawal GIAI, involving adrenocortical cell loss and a superimposed defect in steroidogenesis. We next tested whether preserving adrenal trophic signaling during glucocorticoid exposure could prevent GIAI. Adrenal function recovered more slowly in mice treated with DEX and daily cosyntropin (a synthetic ACTH analog) compared to those treated with DEX alone. In contrast, mice with non-suppressible endogenous ACTH due to targeted hypothalamic deletion of the glucocorticoid receptor maintained normal adrenal architecture and steroidogenic capacity despite prolonged DEX treatment. Pharmacologic treatments that mimic sustained trophic signaling to the adrenal during chronic glucocorticoid treatment may thus prevent GIAI.
| Clave de Referencia |
openalex_W7169579632
Use esta clave para autocitar en el manuscrito mientras usa
SciMatic Manuscript Manager o Thesis Manager
|
|---|---|
| Autores | Lindsey S. Gaston, Brenna C Jorgensen, Hannah R Friedman, Marc S. Sherman, Joseph A. Majzoub |
| Revista | american journal of physiology endocrinology and metabolism |
| Ano | 2026 |
| DOI |
10.1210/endocr/bqag081
|
| URL | |
| Palabras Clave | Palabras clave no encontradas |
Citas
No se encontraron citas. Para agregar una cita, contacte al administrador en info@scimatic.org
Comentarios
Aun no hay comentarios. Sea el primero en comentar este articulo.