2023
Decidualization dampens toll-like receptor mediated inflammatory responses in human endometrial stromal cells by upregulating IκBα
Tong M, Scott J, Whirledge S, Abrahams V. Decidualization dampens toll-like receptor mediated inflammatory responses in human endometrial stromal cells by upregulating IκBα. Journal Of Reproductive Immunology 2023, 159: 103988. PMID: 37451159, PMCID: PMC10530124, DOI: 10.1016/j.jri.2023.103988.Peer-Reviewed Original ResearchConceptsEndometrial stromal cellsInflammatory responseStromal cellsHuman endometrial stromal cellsToll-like receptor signalingSex hormone levelsMenstrual cycle stageToll-like receptorsImmune response changesViral double-stranded RNAHuman EnSCsEndometrial responseProinflammatory cytokinesSuccessful pregnancyMenstrual cycleHuman endometriumHormone levelsMajor cell typesImmune responseNFκB p65Viral infectionDecidualizationBacterial lipopolysaccharideReceptor signalingBacterial components
2021
LOCAL ACTIVATION OF GLUCOCORTICOID SIGNALING IN UTERINE FIBROID CELLS DRIVES GROWTH
Glenn T, Silva E, Suarez P, Flannery C, Whirledge S. LOCAL ACTIVATION OF GLUCOCORTICOID SIGNALING IN UTERINE FIBROID CELLS DRIVES GROWTH. Fertility And Sterility 2021, 116: e419-e420. DOI: 10.1016/j.fertnstert.2021.07.1121.Peer-Reviewed Original ResearchCombinatorial actions of glucocorticoid and mineralocorticoid stress hormone receptors are required for preventing neurodegeneration of the mouse hippocampus
Oakley R, Whirledge S, Petrillo M, Riddick N, Xu X, Moy S, Cidlowski J. Combinatorial actions of glucocorticoid and mineralocorticoid stress hormone receptors are required for preventing neurodegeneration of the mouse hippocampus. Neurobiology Of Stress 2021, 15: 100369. PMID: 34368410, PMCID: PMC8326231, DOI: 10.1016/j.ynstr.2021.100369.Peer-Reviewed Original ResearchDentate gyrus neuronsMineralocorticoid receptorGyrus neuronsKnockout miceSingle knockout counterpartsConditioned fear testDouble knockout miceStress hormone receptorsPrimary stress hormoneCA2 neuronsHippocampal glucocorticoidRelated nuclear receptorsKnockout counterpartsNeuronal deathDentate gyrusNeuronal markersLarge cohortMouse hippocampusPsychiatric disordersGlucocorticoidsHippocampusCell proliferation pathwaysChronic stressStress hormonesProfound neurodegenerationObesity Induces Elevated Oxidative Stress in Uteri of Reproductive Age Mice
Huang J, Xiao E, Tal A, Kelly K, Kim J, Whirledge S, Flannery C. Obesity Induces Elevated Oxidative Stress in Uteri of Reproductive Age Mice. Journal Of The Endocrine Society 2021, 5: a752-a752. DOI: 10.1210/jendso/bvab048.1529.Peer-Reviewed Original ResearchWeeks of dietNC miceHF miceHigher body fatProtein carbonylsOxidative stressAge miceBody fatChronic diet-induced obesityDiet-induced obese miceObesity-related disruptionIndependent risk factorInsulin tolerance testingHigh-fat chowLong-term obesitySeverity of obesityC57BL/6 female miceDiet-induced obesityHigh fat consumptionUterine oxidative stressCYP enzymatic activitiesAge-dependent increaseElevated oxidative stressDNA damageCytochrome P450 expressionChapter 9 Mechanism of glucocorticoid action in immunology—Basic concepts
Wood M, Whirledge S. Chapter 9 Mechanism of glucocorticoid action in immunology—Basic concepts. 2021, 147-170. DOI: 10.1016/b978-0-12-818508-7.00020-8.Peer-Reviewed Original ResearchGlucocorticoid receptorEpigenetic modificationsPosttranslational modificationsTranscription factorsDNA bindingTissue-specific immune responsesOverall physiologyCell typesGlucocorticoid-mediated effectsNuclear receptorsImmune cell typesFundamental processesReceptor isoformsLevels of hormonesRelative expressionReceptor actionReproductive systemChapter 9 MechanismsGlucocorticoid bioavailabilityAutoimmune diseasesGlucocorticoid actionImmune responseFetal developmentCo-FactorImmune system
2019
SAT-005 Gene Expression and Behavioral Alterations in Mice with Conditional Knockout of GR, MR, or Both GR and MR in the Hippocampus
Oakley R, Whirledge S, Riddick N, Quinn M, Xu X, Moy S, Cidlowski J. SAT-005 Gene Expression and Behavioral Alterations in Mice with Conditional Knockout of GR, MR, or Both GR and MR in the Hippocampus. Journal Of The Endocrine Society 2019, 3: sat-005. PMCID: PMC6552087, DOI: 10.1210/js.2019-sat-005.Peer-Reviewed Original ResearchMineralocorticoid receptorDouble knockout miceGlucocorticoid receptorGRKO miceKnockout miceEmx1-Cre miceRelated mineralocorticoid receptorDepression-like behaviorHippocampal glucocorticoid receptorsConditioned fear testOpen field testMonths of agePrimary stress hormoneSwim testPsychiatric disordersUnique signaling pathwaysBehavioral alterationsBody weightCognitive impairmentHippocampusGlucocorticoidsMutant miceStress hormonesBrain functionMiceSUN-019 The Selective Progesterone Receptor Modulator Ulipristal Acetate Blocks Glucocorticoid Receptor Transactivation
Smalls B, Millard C, Kisanga E, Flannery C, Al-Hendy A, Whirledge S. SUN-019 The Selective Progesterone Receptor Modulator Ulipristal Acetate Blocks Glucocorticoid Receptor Transactivation. Journal Of The Endocrine Society 2019, 3: sun-019. PMCID: PMC6553416, DOI: 10.1210/js.2019-sun-019.Peer-Reviewed Original ResearchSelective progesterone receptor modulatorsAnti-glucocorticoid activityUlipristal acetateGlucocorticoid receptorEffect of UPAHuman uterine fibroid tissueLong-term therapeutic agentGR antagonist RU-486Progesterone receptor modulatorsAntagonist RU 486Post-marketing analysisGlucocorticoid-induced expressionLower glucocorticoid receptorUterine fibroid tissueEndogenous glucocorticoid receptorSynthetic glucocorticoid dexamethasoneCell linesUterine fibroid cellsHuman uterine fibroid cellsFemale reproductive systemUtLM cellsHepatic failureLiver injuryPR expressionTherapeutic optionsIn Vitro Assays to Evaluate the Migration, Invasion, and Proliferation of Immortalized Human First-trimester Trophoblast Cell Lines
Kisanga E, Tang Z, Guller S, Whirledge S. In Vitro Assays to Evaluate the Migration, Invasion, and Proliferation of Immortalized Human First-trimester Trophoblast Cell Lines. Journal Of Visualized Experiments 2019 DOI: 10.3791/58942-v.Peer-Reviewed Original ResearchChapter 5 Steroid Hormone Action
Whirledge S, Cidlowski J. Chapter 5 Steroid Hormone Action. 2019, 115-131.e4. DOI: 10.1016/b978-0-323-47912-7.00005-6.Peer-Reviewed Original ResearchSteroid hormone receptorsSteroid hormonesHormone receptorsSteroid hormone actionComplex molecular eventsGroup of hormonesContext-specific mannerPhysiologic responsesNongenomic actionsHormone actionHormoneSignal transductionTranscription factorsReceptorsPhysiologic processesIntracellular proteinsReproductive systemMolecular eventsChemical messengers
2017
Stress and Implantation Failure
Deaton J, Patel B, Johnston-MacAnanny E, Yu J, Whirledge S, Wilson A, David Wininger J, Shu Y, Taylor R, Berga S. Stress and Implantation Failure. 2017, 103-124. DOI: 10.1007/978-3-319-71967-2_7.Peer-Reviewed Original ResearchImplantation failureHCG productionSecretion of estradiolHPO axisMenstrual bleedingOvarian axisEndometrial developmentMetabolic factorsElevated glucocorticoidsEndometriumInappropriate exposureEndocrine signalsLaboratory stressorPutative mechanismsQuantitative exposureImplantationFemale reproductionEstradiolOvulationHealthy blastocystAlterationsFailureExposureBleedingObesityPioneer Factors FOXA1 and FOXA2 Assist Selective Glucocorticoid Receptor Signaling in Human Endometrial Cells
Whirledge S, Kisanga EP, Taylor RN, Cidlowski JA. Pioneer Factors FOXA1 and FOXA2 Assist Selective Glucocorticoid Receptor Signaling in Human Endometrial Cells. Endocrinology 2017, 158: 4076-4092. PMID: 28938408, PMCID: PMC5695839, DOI: 10.1210/en.2017-00361.Peer-Reviewed Original ResearchConceptsPioneer factor FOXA1Polymerase 2Molecular mechanismsRecruitment of GRThousands of genesExpression of lefty1GR-dependent inductionGene expression analysisHuman endometrial cellsGlucocorticoid receptorGlucocorticoid-mediated inductionEndometrial cellsRegulatory regionsGlucocorticoid receptor signalingMaster regulatorSpecific genesExpression analysisPrimary human endometrial cellsGene expressionHuman uterine cellsGlucocorticoid-dependent inductionIntracellular signalingEmbryo implantationFOXA2Receptor recruitmentGenerating diversity in human glucocorticoid signaling through a racially diverse polymorphism in the beta isoform of the glucocorticoid receptor
Whirledge SD, Jewell CM, Barber LM, Xu X, Katen KS, Garantziotis S, Cidlowski JA. Generating diversity in human glucocorticoid signaling through a racially diverse polymorphism in the beta isoform of the glucocorticoid receptor. Laboratory Investigation 2017, 97: 1282-1295. PMID: 28759007, PMCID: PMC5759773, DOI: 10.1038/labinvest.2017.76.Peer-Reviewed Original ResearchMeSH Keywords3' Untranslated RegionsAdultAmino Acid SubstitutionBlack PeopleCell Line, TumorCells, CulturedCohort StudiesFemaleGene Expression RegulationGenetic Association StudiesGlucocorticoidsHispanic or LatinoHumansMacrophagesMaleNorth CarolinaPolymorphism, Single NucleotideProspective StudiesReceptors, GlucocorticoidRecombinant ProteinsRegistriesSignal TransductionWhite PeopleConceptsGene expression profilesGene expressionExpression profilesGlucocorticoid sensitivityT polymorphismWide gene expressionPrimary macrophagesInherent transcriptional activityHigher serum cortisol levelsLow-dose dexamethasoneProspective cohort studyProtein expressionSelf-reported allergiesDominant negative regulatorSerum cortisol levelsReceptor protein expressionSelf-reported diseasesGlucocorticoid receptor geneHuman glucocorticoid receptor geneMinor allele frequencyNon-Hispanic participantsAlternative splicingMRNA stabilityReceptor stabilityTranscriptional activityGlucocorticoids and Reproduction: Traffic Control on the Road to Reproduction
Whirledge S, Cidlowski JA. Glucocorticoids and Reproduction: Traffic Control on the Road to Reproduction. Trends In Endocrinology And Metabolism 2017, 28: 399-415. PMID: 28274682, PMCID: PMC5438761, DOI: 10.1016/j.tem.2017.02.005.Peer-Reviewed Original ResearchConceptsDiverse cellular functionsStress-induced levelsCell-specific mannerCellular functionsGlucocorticoid receptorCellular processingGR geneReproductive functionNormal physiologyActivity of glucocorticoidsCompelling new evidenceReproductionReproductive dysfunctionGlucocorticoid responsivenessGlucocorticoidsSteroid hormonesGenesProteinDiversityPhysiologyRegulationFunctionReceptorsNew evidenceMaintenance
2015
Uterine glucocorticoid receptors are critical for fertility in mice through control of embryo implantation and decidualization
Whirledge SD, Oakley RH, Myers PH, Lydon JP, DeMayo F, Cidlowski JA. Uterine glucocorticoid receptors are critical for fertility in mice through control of embryo implantation and decidualization. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 15166-15171. PMID: 26598666, PMCID: PMC4679013, DOI: 10.1073/pnas.1508056112.Peer-Reviewed Original ResearchConceptsGlucocorticoid receptorPresence of GRExaggerated inflammatory responseSex steroid receptorsImmune cell recruitmentStromal cell decidualizationFemale reproductive tractAdrenal axisKO miceInflammatory responseUterine physiologyUterine biologyEndocrine organMouse uterusBlastocyst implantationGlucocorticoid signalingMouse modelCell recruitmentEmbryo implantationImmunomodulatory functionsKnockout miceGR signalingSteroid receptorsReproductive tractDecidualizationGhrelin Partially Protects Against Cisplatin-Induced Male Murine Gonadal Toxicity in a GHSR-1a-Dependent Manner1
Whirledge SD, Garcia JM, Smith RG, Lamb DJ. Ghrelin Partially Protects Against Cisplatin-Induced Male Murine Gonadal Toxicity in a GHSR-1a-Dependent Manner1. Biology Of Reproduction 2015, 92: 76, 1-11. PMID: 25631345, PMCID: PMC4367966, DOI: 10.1095/biolreprod.114.123570.Peer-Reviewed Original ResearchConceptsTesticular cell deathTesticular damageGonadal toxicityEpididymal weightGrowth hormone secretagogue receptorDose-dependent side effectsCisplatin-induced cachexiaTime of euthanizationHigh cumulative doseBody weight homeostasisCell deathCisplatin-induced testicular damageNovel therapeutic approachesGonadotoxin exposurePermanent azoospermiaGhrelin administrationSubsequent infertilityChemotherapeutic drug cisplatinChemotherapeutic regimensCisplatin administrationGhrelin actionWeight homeostasisCumulative doseIntraperitoneal administrationSecretagogue receptor
2014
Genistein Disrupts Glucocorticoid Receptor Signaling in Human Uterine Endometrial Ishikawa Cells
Whirledge S, Senbanjo LT, Cidlowski JA. Genistein Disrupts Glucocorticoid Receptor Signaling in Human Uterine Endometrial Ishikawa Cells. Environmental Health Perspectives 2014, 123: 80-87. PMID: 25136773, PMCID: PMC4286279, DOI: 10.1289/ehp.1408437.Peer-Reviewed Original ResearchConceptsTarget genesWhole-genome microarray analysisIshikawa cellsGlucocorticoid receptorGenome microarray analysisCommon gene targetsGR target genesTranscriptional responseNumerous genesDisruption of GRTranscriptional antagonismGlucocorticoid receptor signalingEnvironmental estrogen exposureRegulation of stressGene targetsSelect genesGene expressionCoadministration of genisteinEndometrial Ishikawa cellsMicroarray analysisReal-time reverse transcription-polymerase chain reactionFemale reproductive tractReverse transcription-polymerase chain reactionGenesQuantitative real-time reverse transcription-polymerase chain reaction
2013
A Role for Glucocorticoids in Stress-Impaired Reproduction: Beyond the Hypothalamus and Pituitary
Whirledge S, Cidlowski JA. A Role for Glucocorticoids in Stress-Impaired Reproduction: Beyond the Hypothalamus and Pituitary. Endocrinology 2013, 154: 4450-4468. PMID: 24064362, PMCID: PMC3836069, DOI: 10.1210/en.2013-1652.Peer-Reviewed Original ResearchConceptsGlucocorticoid signalingAbsence of stressOffspring fitnessReproductive investmentReproductive successGonadal axisCentral regulatorEvolutionary advantageStress responseReproductive eventsSex steroid receptorsAction of glucocorticoidsReproductive statusReproductionReproductive systemCentral actionAdrenal axisSignalingGlucocorticoid secretionImmune responseGlucocorticoid receptorStress contributesSteroid receptorsGlucocorticoidsMetabolic statusGlobal Gene Expression Analysis in Human Uterine Epithelial Cells Defines New Targets of Glucocorticoid and Estradiol Antagonism1
Whirledge S, Xu X, Cidlowski JA. Global Gene Expression Analysis in Human Uterine Epithelial Cells Defines New Targets of Glucocorticoid and Estradiol Antagonism1. Biology Of Reproduction 2013, 89: 66, 1-17. PMID: 23843231, PMCID: PMC4435104, DOI: 10.1095/biolreprod.113.111054.Peer-Reviewed Original ResearchConceptsImmune systemUterine endometrial cancer cell lineUterine epitheliumEndometrial cancer cell linesHuman uterine epithelial cellsMaintenance of pregnancyEffects of glucocorticoidsImmune cell traffickingSynthetic glucocorticoid dexamethasoneCell linesEpithelial-like cell lineFemale reproductive systemPresence of DexGlucocorticoid-regulated genesIngenuity Pathway AnalysisUterine epithelial cellsCancer cell linesInflammatory responseReproductive hormonesEstrogen receptorGlucocorticoid signalingEmbryo implantationGlucocorticoid dexamethasoneGlucocorticoid receptorGlucocorticoids
2012
Estradiol Antagonism of Glucocorticoid-Induced GILZ Expression in Human Uterine Epithelial Cells and Murine Uterus
Whirledge S, Cidlowski JA. Estradiol Antagonism of Glucocorticoid-Induced GILZ Expression in Human Uterine Epithelial Cells and Murine Uterus. Endocrinology 2012, 154: 499-510. PMID: 23183181, PMCID: PMC3529382, DOI: 10.1210/en.2012-1748.Peer-Reviewed Original ResearchConceptsGILZ gene expressionGILZ expressionEstrogen receptorGlucocorticoid receptorInterplay of estrogensSex hormone signalingEpithelial cellsER antagonist ICIImmune modulating functionsHuman uterine epithelial cellsCombination of dexamethasoneUterine epithelial cellsDexamethasone decreasesImmune-related functionsGlucocorticoid response elementMurine uterusGene expressionMouse uterusGlucocorticoid signalingEmbryo implantationUterine endometriumGILZ promoterGlucocorticoidsHormone treatmentReceptorsGlucocorticoids Regulate Gene Expression and Repress Cellular Proliferation in Human Uterine Leiomyoma Cells
Whirledge S, Dixon D, Cidlowski JA. Glucocorticoids Regulate Gene Expression and Repress Cellular Proliferation in Human Uterine Leiomyoma Cells. Discover Oncology 2012, 3: 79-92. PMID: 22311344, PMCID: PMC4772901, DOI: 10.1007/s12672-012-0103-0.Peer-Reviewed Original ResearchConceptsUterine leiomyoma cellsHuman uterine leiomyoma cellsLeiomyoma cellsGlucocorticoid receptorUterine leiomyomaUterine leiomyoma treatmentAbsence of estrogenPotential roleSmooth muscle cellsSynthetic glucocorticoid dexamethasoneIngenuity Pathway AnalysisLeiomyoma treatmentSignificant glucocorticoidE2 effectsEstrogen treatmentCell growthSex hormonesGenome-wide microarray studiesGlucocorticoid dexamethasoneGlucocorticoidsS-phase cellsNormal myometriumFlow cytometryMuscle cellsLeiomyoma