{"data":{"id":"10.5061/dryad.1g1jwsvd0","type":"dois","attributes":{"doi":"10.5061/dryad.1g1jwsvd0","prefix":"10.5061","suffix":"dryad.1g1jwsvd0","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"Gaston, Lindsey","nameType":"Personal","affiliation":["Boston Children's Hospital"],"nameIdentifiers":[{"schemeUri":"https://orcid.org","nameIdentifier":"https://orcid.org/0000-0003-3486-7254","nameIdentifierScheme":"ORCID"}]},{"name":"Jorgensen, Brenna","nameType":"Personal","affiliation":["Boston Children's Hospital"],"nameIdentifiers":[]},{"name":"Friedman, Hannah","nameType":"Personal","affiliation":["Boston Children's Hospital"],"nameIdentifiers":[]},{"name":"Sherman, Marc","nameType":"Personal","affiliation":["Massachusetts General Hospital"],"nameIdentifiers":[]},{"name":"Majzoub, Joseph","nameType":"Personal","affiliation":["Boston Children's Hospital"],"nameIdentifiers":[]}],"titles":[{"title":"Adrenal rather than central dysfunction limits HPA axis recovery after chronic glucocorticoid treatment in male mice"}],"publisher":"Dryad","container":{},"publicationYear":2026,"subjects":[{"subject":"FOS: Biological sciences","schemeUri":"https://web-archive.oecd.org/2012-06-15/138575-38235147.pdf","subjectScheme":"fos"},{"subject":"FOS: Basic medicine","schemeUri":"https://web-archive.oecd.org/2012-06-15/138575-38235147.pdf","subjectScheme":"fos"},{"subject":"Endocrinology","schemeUri":"https://github.com/PLOS/plos-thesaurus","subjectScheme":"PLOS Subject Area Thesaurus"},{"subject":"Adrenal glands","schemeUri":"https://github.com/PLOS/plos-thesaurus","subjectScheme":"PLOS Subject Area Thesaurus"},{"subject":"Glucocorticoid therapy","schemeUri":"https://github.com/PLOS/plos-thesaurus","subjectScheme":"PLOS Subject Area Thesaurus"}],"contributors":[],"dates":[{"date":"2026-06-15T17:53:24Z","dateType":"Created"},{"date":"2026-06-15T17:56:17Z","dateType":"Submitted"},{"date":"2026-07-09T00:00:00Z","dateType":"Issued"},{"date":"2026-07-09T00:00:00Z","dateType":"Available"}],"language":"en","types":{"ris":"DATA","bibtex":"misc","citeproc":"dataset","schemaOrg":"Dataset","resourceType":"dataset","resourceTypeGeneral":"Dataset"},"relatedIdentifiers":[{"relationType":"IsCitedBy","relatedIdentifier":"10.1101/2025.04.30.651350","relatedIdentifierType":"DOI"},{"relationType":"IsCitedBy","relatedIdentifier":"10.1210/endocr/bqag081","relatedIdentifierType":"DOI"}],"relatedItems":[],"sizes":["51068 bytes"],"formats":[],"version":"4","rightsList":[{"rights":"Creative Commons Zero v1.0 Universal","rightsUri":"https://creativecommons.org/publicdomain/zero/1.0/legalcode","schemeUri":"https://spdx.org/licenses/","rightsIdentifier":"cc0-1.0","rightsIdentifierScheme":"SPDX"}],"descriptions":[{"description":"Glucocorticoid-induced adrenal insufficiency (GIAI) can persist for months\n after discontinuation of chronic corticosteroid therapy, placing patients\n at risk for life-threatening adrenal crises. This prolonged suppression\n has been attributed primarily to delayed restoration of\n hypothalamic–pituitary signaling based on indirect measures of central\n axis activity. To identify the rate-limiting site of\n hypothalamic-pituitary-adrenal (HPA) axis recovery, we evaluated the\n timing of functional and histologic recovery at each node of the axis\n following 8 weeks of dexamethasone (DEX) treatment in adult, male mice.\n DEX administration fully suppressed HPA axis activity. Unexpectedly,\n within one week of DEX withdrawal, hypothalamic Crh mRNA\n and plasma ACTH rebounded above control levels, whereas corticosterone\n (CORT) remained suppressed for an additional seven weeks. DEX-treated\n adrenals were markedly atrophic and contained large clusters of\n lipid-filled macrophages. Even after adjusting for macrophage content,\n CORT secretion was disproportionately low relative to the remaining\n adrenocortical cell mass despite supraphysiologic ACTH stimulation. The\n adrenal is thus the principal site of post-withdrawal GIAI, involving\n adrenocortical cell loss and a superimposed defect in steroidogenesis. We\n next tested whether preserving adrenal trophic signaling during\n glucocorticoid exposure could prevent GIAI. Adrenal function recovered\n more slowly in mice treated with DEX and daily cosyntropin (a synthetic\n ACTH analog) compared to those treated with DEX alone. In contrast, mice\n with non-suppressible endogenous ACTH due to targeted hypothalamic\n deletion of the glucocorticoid receptor maintained normal adrenal\n architecture and steroidogenic capacity despite prolonged DEX treatment.\n Pharmacologic treatments that mimic sustained trophic signaling to the\n adrenal during chronic glucocorticoid treatment may thus prevent GIAI.","descriptionType":"Abstract"},{"description":"# Adrenal rather than central dysfunction limits HPA axis recovery after\n chronic glucocorticoid treatment in male mice Dataset DOI:\n [10.5061/dryad.1g1jwsvd0](https://doi.org/10.5061/dryad.1g1jwsvd0) ##\n Description of the data and file structure This dataset contains the raw\n numerical data underlying all quantitative figures in a study\n characterizing the site and mechanisms of glucocorticoid-induced adrenal\n insufficiency (GIAI) in a murine model. Adult male C57BL/6J mice were\n treated with dexamethasone (DEX) via drinking water for 8 weeks, followed\n by serial assessment of hypothalamic-pituitary-adrenal (HPA) axis function\n and adrenal histology at 1–2 week intervals through 8 weeks\n post-withdrawal. Outcome measures included hypothalamic *Crh* mRNA\n expression (quantified by RNAScope densitometry), plasma ACTH and\n corticosterone concentrations following insulin-induced hypoglycemia and\n cosyntropin stimulation (measured by ELISA), adrenal gland weights,\n morphometric quantification of adrenocortical and adrenal macrophage area\n (by fluorescence microscopy and QuPath image analysis), steroidogenic\n pathway gene expression per zona fasciculata cell (by multiplexed\n fluorescent RNAScope and QuPath puncta counting), and adrenocortical\n proliferation and zona glomerulosa thickness. Two intervention paradigms\n were additionally studied: pharmacologic co-treatment with daily\n cosyntropin during DEX exposure, and a genetic model of sustained\n endogenous ACTH secretion during DEX treatment (Sim1Cre:GRfl/fl mice, or\n HGRKO). ### Files and variables #### File: Supporting_data_raw.xlsx\n **Description:**  This file contains 34 worksheets. Each worksheet\n corresponds to one quantitative panel of a main or supplemental figure in\n the manuscript. Worksheet names indicate the figure panel (e.g.,\n \"Fig. 1B\" contains the raw data plotted in Figure 1B). Each\n column represents one experimental group and each row represents one\n biological replicate (individual mouse). **Abbreviations and variables:**\n * DN — Dexamethasone-naïve (vehicle-treated control) * DEX — Dexamethasone\n * COS — Cosyntropin (synthetic ACTH[1-24]) * DEX+COS — Combined\n dexamethasone and daily cosyntropin treatment * 4D DEX — 4 days of\n dexamethasone treatment * 4D DEX+COS — 4 days of combined dexamethasone\n and cosyntropin treatment 8+0, 8+1, 8+2, etc. — 8 weeks of DEX treatment\n followed by 0, 1, 2, etc. weeks post-withdrawal * HGRWT — Cre-negative\n littermate control mice (functionally wild-type) * HGRKO —\n Sim1Cre:GR*fl/fl* mice with selective hypothalamic glucocorticoid receptor\n deletion * ACTH — Adrenocorticotropic hormone (pg/mL; measured by two-site\n sandwich ELISA, ALPCO #21-ACTHU-E01) * CORT — Corticosterone (µg/dL;\n measured by competitive ELISA, ALPCO #55-CORMS-E01) * IIH —\n Insulin-induced hypoglycemia (stressor used to stimulate HPA axis) * AU —\n Arbitrary units (normalized to the dexamethasone-naïve control mean, set\n to 1.0, unless otherwise specified) * zF — Zona fasciculata * zG — Zona\n glomerulosa * PVH — Paraventricular nucleus of the hypothalamus * AM —\n Adrenal macrophage **Worksheet descriptions:** * *Fig 1B* — *Crh* mRNA\n expression (AU) in the PVH at DN, 8+0, and 8+1, quantified by chromogenic\n RNAScope densitometry (Weka Segmentation plugin, Fiji ImageJ) and\n normalized to DN controls  * *Fig. 1C* — IIH-stimulated plasma ACTH\n (pg/mL) at DN, 8+0, 8+1, 8+2, 8+3, 8+4, 8+6, and 8+8. * *Fig. 1D* —\n IIH-stimulated plasma CORT (µg/dL) at DN, 8+0, 8+1, 8+2, 8+3, 8+4, 8+6,\n and 8+8. * *Fig. 1E* — Cosyntropin-stimulated plasma CORT (µg/dL) at DN,\n 8+0, 8+1, 8+2, 8+3, 8+4, 8+6, and 8+8. * *Fig. 2A* — Adrenal gland weight\n (mg) at DN, 8+0, 8+1, 8+2, 8+6, and 8+8. * *Fig. 3B* — Pan-cortical area\n (µm²; streptavidin-positive plus autofluorescent regions) at DN, 8+0, 8+1,\n 8+2, 8+6, and 8+8, from morphometric analysis of thick floating adrenal\n sections in QuPath. * *Fig. 3C* — Medullary (tyrosine\n hydroxylase-positive) area (µm²) at DN, 8+0, 8+1, 8+2, 8+6, and 8+8; used\n to confirm equivalent sectioning across timepoints. * *Fig. 3D* —\n Autofluorescent adrenal macrophage (AM) area (µm²) at DN, 8+0, 8+1, 8+2,\n 8+6, and 8+8. * *Fig. 3E* — Steroidogenic cell type area (µm²) at DN, 8+0,\n 8+1, 8+2, 8+6, and 8+8; computed by subtracting AM area from pan-cortical\n area. * *Fig. 3F* — Ratio of cosyntropin-stimulated CORT to steroidogenic\n cell type area, normalized to DN (AU), at DN, 8+0, 8+1, 8+2, 8+6, and 8+8.\n * *Fig. 4F* — *Mc2r* mRNA puncta per zF cell (AU, normalized to DN) at DN,\n 8+0, and 8+1; quantified by multiplexed fluorescent RNAScope and QuPath\n subcellular detection. * *Fig. 4G* — *Star* mRNA puncta per zF cell (AU)\n at DN, 8+0, and 8+1. * *Fig. 4H* — *Cyp11a1* mRNA puncta per zF cell (AU)\n at DN, 8+0, and 8+1. * *Fig. 4I* — *Hsd3b2* mRNA puncta per zF cell (AU)\n at DN, 8+0, and 8+1. * *Fig. 4J* — *Cyp11b1* mRNA puncta per zF cell (AU)\n at DN, 8+0, and 8+1. * *Fig. 5B* — Percentage of TUNEL-positive\n adrenocortical cells (%) in DN, 4D DEX, and 4D DEX+COS adrenals;\n quantified by QuPath positive cell detection. * *Fig. 5C* —\n Cosyntropin-stimulated CORT (µg/dL) over 0–8 weeks post-withdrawal in\n DEX-treated and DEX+COS-treated mice, with DN reference values. Columns:\n weeks post-withdrawal (X), individual DEX-treated mice, individual\n DEX+COS-treated mice, DN reference mice. * *Fig. 5E* — Pan-cortical area\n normalized to DN (AU) in 8+1 DEX-monotherapy and 8+1 DEX+COS adrenals. *\n *Fig. 5F* — AM area (µm²) in 8+1 DEX-monotherapy and 8+1 DEX+COS adrenals.\n * *Fig. 5G* — Steroidogenic cell type area normalized to DN (AU) in 8+1\n DEX-monotherapy and 8+1 DEX+COS adrenals. * *Fig. 6B* — Percentage of\n GR-immunoreactive nuclei (%) in the PVH of DEX-treated HGRWT and HGRKO\n mice. * *Fig. 6D* — *Crh* mRNA expression (AU) in the PVH of DEX-treated\n HGRWT and HGRKO mice, quantified by chromogenic RNAScope densitometry\n (Weka Segmentation plugin, Fiji ImageJ); not normalized. * *Fig. 7B* —\n Percentage of TUNEL-positive adrenocortical cells (%) in DN, 4D DEX (WT),\n and 4D DEX HGRKO adrenals. * *Fig. 7C* — Basal plasma ACTH (pg/mL) in\n HGRWT and HGRKO mice prior to DEX treatment and on 8 weeks of DEX (8+0). *\n *Fig. 7D* — Plasma CORT (µg/dL) in HGRWT and HGRKO mice under basal,\n restraint-stimulated, and cosyntropin-stimulated conditions, both prior to\n DEX and on 8 weeks of DEX (8+0). * *Fig. 7E* — Adrenal weights (mg) in\n HGRWT and HGRKO mice on long-term DEX (8+0). * *Fig. 7F* — Pan-cortical\n area normalized to DN (AU) in HGRWT and HGRKO adrenals at 8+0. * *Fig. 7G*\n — AM area (µm²) in HGRWT and HGRKO adrenals at 8+0. * *Fig. 7H* —\n Steroidogenic cell type area normalized to DN (AU) in HGRWT and HGRKO\n adrenals at 8+0. * *Fig. 8D* — *Mc2r* mRNA puncta per zF cell (AU,\n normalized to DN) in DN controls, WT 4D DEX, WT 4D DEX+COS, and HGRKO 4D\n DEX adrenals. * *Fig. S2A* — Adrenal weight (% of DN mean) and\n IIH-stimulated CORT (% of DN mean) over the post-withdrawal time course;\n derived from Figs. 2A and 1D respectively. * *Fig. S2B* — Adrenal weight\n (% of DN mean) and cosyntropin-stimulated CORT (% of DN mean) over the\n post-withdrawal time course; derived from Figs. 2A and 1E respectively. *\n *Fig. S5C* — Zona glomerulosa thickness (µm) in DN, 8+0, and 8+1 adrenals,\n measured from Dab2 immunofluorescence images. * *Fig. S5D* — Percentage of\n Ki-67-positive adrenocortical cells (%) in DN, 8+0, and 8+1 adrenals,\n quantified by QuPath positive cell detection. ## Code/software No custom\n code or scripts are included with this submission. The raw data file\n (Supporting_data_raw.xlsx) can be opened with any spreadsheet software\n capable of reading .xlsx format, including Microsoft Excel, Google Sheets,\n or the free, open-source application LibreOffice Calc (available at\n libreoffice.org). Statistical analyses were performed in GraphPad Prism\n v10.3.1 (GraphPad Software, Boston, MA; graphpad.com). Prism project files\n are not included in this deposit, but statistical tests applied to each\n variable and summary statistics are reported in the manuscript text and\n figure legends. Assumptions for parametric testing are fully reported\n in Supplemental Table SIII of the manuscript. Image quantification was\n performed using QuPath v0.4.3 (qupath.github.io), a free, open-source\n digital pathology platform. Hypothalamic *Crh* mRNA densitometry was\n performed in Fiji ImageJ (fiji.sc) using the Weka Segmentation plugin. No\n QuPath or ImageJ project files are included in this deposit, as the\n underlying quantitative outputs are provided in full in the accompanying\n spreadsheet.","descriptionType":"TechnicalInfo"}],"geoLocations":[],"fundingReferences":[{"awardUri":"https://reporter.nih.gov/project-details/11372047","awardTitle":"\n        Mechanisms of hypothalamic-pituitary-adrenal axis suppression and\n        recovery after long-term glucocorticoids\n      ","funderName":"National Institute of Diabetes and Digestive and Kidney Diseases","awardNumber":"1K08DK142004-01A1","funderIdentifier":"https://ror.org/00adh9b73","funderIdentifierType":"ROR"}],"xml":"<?xml version="1.0" encoding="UTF-8"?>
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      <creatorName nameType="Personal">Gaston, Lindsey</creatorName>
      <nameIdentifier nameIdentifierScheme="ORCID" schemeURI="http://orcid.org/">0000-0003-3486-7254</nameIdentifier>
      <affiliation affiliationIdentifier="https://ror.org/00dvg7y05" affiliationIdentifierScheme="ROR" schemeURI="https://ror.org">Boston Children's Hospital</affiliation>
    </creator>
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      <creatorName nameType="Personal">Jorgensen, Brenna</creatorName>
      <affiliation affiliationIdentifier="https://ror.org/00dvg7y05" affiliationIdentifierScheme="ROR" schemeURI="https://ror.org">Boston Children's Hospital</affiliation>
    </creator>
    <creator>
      <creatorName nameType="Personal">Friedman, Hannah</creatorName>
      <affiliation affiliationIdentifier="https://ror.org/00dvg7y05" affiliationIdentifierScheme="ROR" schemeURI="https://ror.org">Boston Children's Hospital</affiliation>
    </creator>
    <creator>
      <creatorName nameType="Personal">Sherman, Marc</creatorName>
      <affiliation affiliationIdentifier="https://ror.org/002pd6e78" affiliationIdentifierScheme="ROR" schemeURI="https://ror.org">Massachusetts General Hospital</affiliation>
    </creator>
    <creator>
      <creatorName nameType="Personal">Majzoub, Joseph</creatorName>
      <affiliation affiliationIdentifier="https://ror.org/00dvg7y05" affiliationIdentifierScheme="ROR" schemeURI="https://ror.org">Boston Children's Hospital</affiliation>
    </creator>
  </creators>
  <titles>
    <title>
      Adrenal rather than central dysfunction limits HPA axis recovery after
      chronic glucocorticoid treatment in male mice
    </title>
  </titles>
  <publisher publisherIdentifier="https://ror.org/00x6h5n95" publisherIdentifierScheme="ROR" schemeURI="https://ror.org/">Dryad</publisher>
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  <publicationYear>2026</publicationYear>
  <subjects>
    <subject subjectScheme="fos" schemeURI="https://web-archive.oecd.org/2012-06-15/138575-38235147.pdf">FOS: Biological sciences</subject>
    <subject subjectScheme="fos" schemeURI="https://web-archive.oecd.org/2012-06-15/138575-38235147.pdf">FOS: Basic medicine</subject>
    <subject subjectScheme="PLOS Subject Area Thesaurus" schemeURI="https://github.com/PLOS/plos-thesaurus">Endocrinology</subject>
    <subject subjectScheme="PLOS Subject Area Thesaurus" schemeURI="https://github.com/PLOS/plos-thesaurus">Adrenal glands</subject>
    <subject subjectScheme="PLOS Subject Area Thesaurus" schemeURI="https://github.com/PLOS/plos-thesaurus">Glucocorticoid therapy</subject>
  </subjects>
  <fundingReferences>
    <fundingReference>
      <funderName>National Institute of Diabetes and Digestive and Kidney Diseases</funderName>
      <funderIdentifier funderIdentifierType="ROR">https://ror.org/00adh9b73</funderIdentifier>
      <awardNumber awardURI="https://reporter.nih.gov/project-details/11372047">1K08DK142004-01A1</awardNumber>
      <awardTitle>
        Mechanisms of hypothalamic-pituitary-adrenal axis suppression and
        recovery after long-term glucocorticoids
      </awardTitle>
    </fundingReference>
  </fundingReferences>
  <dates>
    <date dateType="Created">2026-06-15T17:53:24Z</date>
    <date dateType="Submitted">2026-06-15T17:56:17Z</date>
    <date dateType="Issued">2026-07-09T00:00:00Z</date>
    <date dateType="Available">2026-07-09T00:00:00Z</date>
  </dates>
  <language>en</language>
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    <relatedIdentifier relationType="IsCitedBy" relatedIdentifierType="DOI">https://doi.org/10.1210/endocr/bqag081</relatedIdentifier>
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  <descriptions>
    <description descriptionType="Abstract">
      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&amp;nbsp;Crh&amp;nbsp;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.
    </description>
    <description descriptionType="TechnicalInfo">
      # Adrenal rather than central dysfunction limits HPA axis recovery after
      chronic glucocorticoid treatment in male mice Dataset DOI:
      [10.5061/dryad.1g1jwsvd0](https://doi.org/10.5061/dryad.1g1jwsvd0) ##
      Description of the data and file structure This dataset contains the raw
      numerical data underlying all quantitative figures in a study
      characterizing the site and mechanisms of glucocorticoid-induced adrenal
      insufficiency (GIAI) in a murine model. Adult male C57BL/6J mice were
      treated with dexamethasone (DEX) via drinking water for 8 weeks, followed
      by serial assessment of hypothalamic-pituitary-adrenal (HPA) axis function
      and adrenal histology at 1–2 week intervals through 8 weeks
      post-withdrawal. Outcome measures included hypothalamic *Crh* mRNA
      expression (quantified by RNAScope densitometry), plasma ACTH and
      corticosterone concentrations following insulin-induced hypoglycemia and
      cosyntropin stimulation (measured by ELISA), adrenal gland weights,
      morphometric quantification of adrenocortical and adrenal macrophage area
      (by fluorescence microscopy and QuPath image analysis), steroidogenic
      pathway gene expression per zona fasciculata cell (by multiplexed
      fluorescent RNAScope and QuPath puncta counting), and adrenocortical
      proliferation and zona glomerulosa thickness. Two intervention paradigms
      were additionally studied: pharmacologic co-treatment with daily
      cosyntropin during DEX exposure, and a genetic model of sustained
      endogenous ACTH secretion during DEX treatment (Sim1Cre:GRfl/fl mice, or
      HGRKO). ### Files and variables #### File: Supporting_data_raw.xlsx
      **Description:**  This file contains 34 worksheets. Each worksheet
      corresponds to one quantitative panel of a main or supplemental figure in
      the manuscript. Worksheet names indicate the figure panel (e.g.,
      "Fig. 1B" contains the raw data plotted in Figure 1B). Each
      column represents one experimental group and each row represents one
      biological replicate (individual mouse). **Abbreviations and variables:**
      * DN — Dexamethasone-naïve (vehicle-treated control) * DEX — Dexamethasone
      * COS — Cosyntropin (synthetic ACTH[1-24]) * DEX+COS — Combined
      dexamethasone and daily cosyntropin treatment * 4D DEX — 4 days of
      dexamethasone treatment * 4D DEX+COS — 4 days of combined dexamethasone
      and cosyntropin treatment 8+0, 8+1, 8+2, etc. — 8 weeks of DEX treatment
      followed by 0, 1, 2, etc. weeks post-withdrawal * HGRWT — Cre-negative
      littermate control mice (functionally wild-type) * HGRKO —
      Sim1Cre:GR*fl/fl* mice with selective hypothalamic glucocorticoid receptor
      deletion * ACTH — Adrenocorticotropic hormone (pg/mL; measured by two-site
      sandwich ELISA, ALPCO #21-ACTHU-E01) * CORT — Corticosterone (µg/dL;
      measured by competitive ELISA, ALPCO #55-CORMS-E01) * IIH —
      Insulin-induced hypoglycemia (stressor used to stimulate HPA axis) * AU —
      Arbitrary units (normalized to the dexamethasone-naïve control mean, set
      to 1.0, unless otherwise specified) * zF — Zona fasciculata * zG — Zona
      glomerulosa * PVH — Paraventricular nucleus of the hypothalamus * AM —
      Adrenal macrophage **Worksheet descriptions:** * *Fig 1B* — *Crh* mRNA
      expression (AU) in the PVH at DN, 8+0, and 8+1, quantified by chromogenic
      RNAScope densitometry (Weka Segmentation plugin, Fiji ImageJ) and
      normalized to DN controls  * *Fig. 1C* — IIH-stimulated plasma ACTH
      (pg/mL) at DN, 8+0, 8+1, 8+2, 8+3, 8+4, 8+6, and 8+8. * *Fig. 1D* —
      IIH-stimulated plasma CORT (µg/dL) at DN, 8+0, 8+1, 8+2, 8+3, 8+4, 8+6,
      and 8+8. * *Fig. 1E* — Cosyntropin-stimulated plasma CORT (µg/dL) at DN,
      8+0, 8+1, 8+2, 8+3, 8+4, 8+6, and 8+8. * *Fig. 2A* — Adrenal gland weight
      (mg) at DN, 8+0, 8+1, 8+2, 8+6, and 8+8. * *Fig. 3B* — Pan-cortical area
      (µm²; streptavidin-positive plus autofluorescent regions) at DN, 8+0, 8+1,
      8+2, 8+6, and 8+8, from morphometric analysis of thick floating adrenal
      sections in QuPath. * *Fig. 3C* — Medullary (tyrosine
      hydroxylase-positive) area (µm²) at DN, 8+0, 8+1, 8+2, 8+6, and 8+8; used
      to confirm equivalent sectioning across timepoints. * *Fig. 3D* —
      Autofluorescent adrenal macrophage (AM) area (µm²) at DN, 8+0, 8+1, 8+2,
      8+6, and 8+8. * *Fig. 3E* — Steroidogenic cell type area (µm²) at DN, 8+0,
      8+1, 8+2, 8+6, and 8+8; computed by subtracting AM area from pan-cortical
      area. * *Fig. 3F* — Ratio of cosyntropin-stimulated CORT to steroidogenic
      cell type area, normalized to DN (AU), at DN, 8+0, 8+1, 8+2, 8+6, and 8+8.
      * *Fig. 4F* — *Mc2r* mRNA puncta per zF cell (AU, normalized to DN) at DN,
      8+0, and 8+1; quantified by multiplexed fluorescent RNAScope and QuPath
      subcellular detection. * *Fig. 4G* — *Star* mRNA puncta per zF cell (AU)
      at DN, 8+0, and 8+1. * *Fig. 4H* — *Cyp11a1* mRNA puncta per zF cell (AU)
      at DN, 8+0, and 8+1. * *Fig. 4I* — *Hsd3b2* mRNA puncta per zF cell (AU)
      at DN, 8+0, and 8+1. * *Fig. 4J* — *Cyp11b1* mRNA puncta per zF cell (AU)
      at DN, 8+0, and 8+1. * *Fig. 5B* — Percentage of TUNEL-positive
      adrenocortical cells (%) in DN, 4D DEX, and 4D DEX+COS adrenals;
      quantified by QuPath positive cell detection. * *Fig. 5C* —
      Cosyntropin-stimulated CORT (µg/dL) over 0–8 weeks post-withdrawal in
      DEX-treated and DEX+COS-treated mice, with DN reference values. Columns:
      weeks post-withdrawal (X), individual DEX-treated mice, individual
      DEX+COS-treated mice, DN reference mice. * *Fig. 5E* — Pan-cortical area
      normalized to DN (AU) in 8+1 DEX-monotherapy and 8+1 DEX+COS adrenals. *
      *Fig. 5F* — AM area (µm²) in 8+1 DEX-monotherapy and 8+1 DEX+COS adrenals.
      * *Fig. 5G* — Steroidogenic cell type area normalized to DN (AU) in 8+1
      DEX-monotherapy and 8+1 DEX+COS adrenals. * *Fig. 6B* — Percentage of
      GR-immunoreactive nuclei (%) in the PVH of DEX-treated HGRWT and HGRKO
      mice. * *Fig. 6D* — *Crh* mRNA expression (AU) in the PVH of DEX-treated
      HGRWT and HGRKO mice, quantified by chromogenic RNAScope densitometry
      (Weka Segmentation plugin, Fiji ImageJ); not normalized. * *Fig. 7B* —
      Percentage of TUNEL-positive adrenocortical cells (%) in DN, 4D DEX (WT),
      and 4D DEX HGRKO adrenals. * *Fig. 7C* — Basal plasma ACTH (pg/mL) in
      HGRWT and HGRKO mice prior to DEX treatment and on 8 weeks of DEX (8+0). *
      *Fig. 7D* — Plasma CORT (µg/dL) in HGRWT and HGRKO mice under basal,
      restraint-stimulated, and cosyntropin-stimulated conditions, both prior to
      DEX and on 8 weeks of DEX (8+0). * *Fig. 7E* — Adrenal weights (mg) in
      HGRWT and HGRKO mice on long-term DEX (8+0). * *Fig. 7F* — Pan-cortical
      area normalized to DN (AU) in HGRWT and HGRKO adrenals at 8+0. * *Fig. 7G*
      — AM area (µm²) in HGRWT and HGRKO adrenals at 8+0. * *Fig. 7H* —
      Steroidogenic cell type area normalized to DN (AU) in HGRWT and HGRKO
      adrenals at 8+0. * *Fig. 8D* — *Mc2r* mRNA puncta per zF cell (AU,
      normalized to DN) in DN controls, WT 4D DEX, WT 4D DEX+COS, and HGRKO 4D
      DEX adrenals. * *Fig. S2A* — Adrenal weight (% of DN mean) and
      IIH-stimulated CORT (% of DN mean) over the post-withdrawal time course;
      derived from Figs. 2A and 1D respectively. * *Fig. S2B* — Adrenal weight
      (% of DN mean) and cosyntropin-stimulated CORT (% of DN mean) over the
      post-withdrawal time course; derived from Figs. 2A and 1E respectively. *
      *Fig. S5C* — Zona glomerulosa thickness (µm) in DN, 8+0, and 8+1 adrenals,
      measured from Dab2 immunofluorescence images. * *Fig. S5D* — Percentage of
      Ki-67-positive adrenocortical cells (%) in DN, 8+0, and 8+1 adrenals,
      quantified by QuPath positive cell detection. ## Code/software No custom
      code or scripts are included with this submission. The raw data file
      (Supporting_data_raw.xlsx) can be opened with any spreadsheet software
      capable of reading .xlsx format, including Microsoft Excel, Google Sheets,
      or the free, open-source application LibreOffice Calc (available at
      libreoffice.org). Statistical analyses were performed in GraphPad Prism
      v10.3.1 (GraphPad Software, Boston, MA; graphpad.com). Prism project files
      are not included in this deposit, but statistical tests applied to each
      variable and summary statistics are reported in the manuscript text and
      figure legends. Assumptions for parametric testing are fully reported
      in Supplemental Table SIII of the manuscript. Image quantification was
      performed using QuPath v0.4.3 (qupath.github.io), a free, open-source
      digital pathology platform. Hypothalamic *Crh* mRNA densitometry was
      performed in Fiji ImageJ (fiji.sc) using the Weka Segmentation plugin. No
      QuPath or ImageJ project files are included in this deposit, as the
      underlying quantitative outputs are provided in full in the accompanying
      spreadsheet.
    </description>
  </descriptions>
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