2023
Estradiol cycling drives female obesogenic adipocyte hyperplasia
del M. Saavedra-Peña R, Taylor N, Flannery C, Rodeheffer M. Estradiol cycling drives female obesogenic adipocyte hyperplasia. Cell Reports 2023, 42: 112390. PMID: 37053070, PMCID: PMC10567995, DOI: 10.1016/j.celrep.2023.112390.Peer-Reviewed Original ResearchConceptsAdipocyte precursor cellsHigh-fat dietAdipocyte hyperplasiaHFD feedingVisceral WATDifferential fat distributionAdipose tissue distributionEstrogen receptor αWAT distributionFat distributionOvariectomized femalesHyperplasiaMice showEstrous cycleReceptor αTissue distributionPrecursor cellsObesityAPC proliferationTissue microenvironmentProliferationFemalesSexOnsetFeeding
2022
Hyperinsulinemia induces early and dyssynchronous puberty in lean female mice.
Saleh FL, Joshi AA, Tal A, Xu P, Hens J, Wong SL, Flannery C. Hyperinsulinemia induces early and dyssynchronous puberty in lean female mice. Journal Of Endocrinology 2022, 254: 121-135. PMID: 35904489, PMCID: PMC9837806, DOI: 10.1530/joe-21-0447.Peer-Reviewed Original ResearchConceptsVaginal openingInsulin resistanceDay of VOIGF-1 levelsInsulin-like growth factor 1 receptorGreater insulin resistanceHigher insulin levelsEffect of hyperinsulinemiaGrowth factor 1 receptorGonadotropin-releasing hormoneLower body weightFactor 1 receptorReceptor isoform expressionMammary gland developmentLH levelsInsulin levelsInsulin receptor isoform expressionKisspeptin expressionChildhood obesityFemale miceHormone levelsEarly initiationHyperinsulinemiaBody weightOvarian follicles
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 ResearchIdentification of Cellular Damage in Uteri From Hyperinsulinemic Mice Treated With Unopposed Estradiol
Kelly K, Huang J, Joshi A, Tal A, Wong S, Flannery C. Identification of Cellular Damage in Uteri From Hyperinsulinemic Mice Treated With Unopposed Estradiol. Journal Of The Endocrine Society 2021, 5: a750-a751. DOI: 10.1210/jendso/bvab048.1526.Peer-Reviewed Original ResearchUnopposed estradiolWT miceMKR miceEndometrial adenocarcinomaNuclear atypiaExact testPlacebo-treated miceSetting of hyperinsulinemiaInsulin tolerance testingNormal-weight womenSetting of obesityEffects of estradiolCohort of miceFischer's exact testLower body weightOxidative stress-induced damagePercent body fatDNA damageBlinded histological analysisPartial hysterectomyWeight womenAnovulatory cyclesEndometrial glandsHyperinsulinemic miceCystic dilationObesity 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 expression
2019
SAT-LB041 Insulin and IGF-2 Equally Regulate Placental Triglyceride Content
Anam A, Cooke K, O'Bryan J, Flannery C. SAT-LB041 Insulin and IGF-2 Equally Regulate Placental Triglyceride Content. Journal Of The Endocrine Society 2019, 3: sat-lb041. PMCID: PMC6552031, DOI: 10.1210/js.2019-sat-lb041.Peer-Reviewed Original ResearchPlacental lipid metabolismLean womenIGF-2Triglyceride contentLipid metabolismIGF-1Maternal triglyceride levelsMean age 34.4Elective C-sectionTime of presentationInsulin receptor isoformsMultiple comparison testColorimetric spectrophotometerNeonatal complicationsPlacenta explantsMaternal obesityNeonatal adiposityPlacental lipid contentMaternal insulinObese womenPregnant womenTG levelsTriglyceride levelsEndocrine SocietyVillous explantsSUN-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 options
2018
Postmenopausal Women with Endometrial Cancer Have Greater Metabolic Dysfunction and Higher BMI than Women with Benign Endometrium
COOKE K, DUN E, ANAM A, FLANNERY C. Postmenopausal Women with Endometrial Cancer Have Greater Metabolic Dysfunction and Higher BMI than Women with Benign Endometrium. Diabetes 2018, 67 DOI: 10.2337/db18-302-lb.Peer-Reviewed Original ResearchEndometrial adenocarcinomaType 2 diabetesBenign hyperplasiaPostmenopausal womenBMI distributionEC pathogenesisMore premenopausal womenRole of obesityIndependent risk factorWomen age 50T-testStudent's t-testBMI 25Premenopausal womenLow HDLObese womenEndometrial cancerHigh triglyceridesTotal cholesterolHigher BMIMetabolic abnormalitiesProspective studyBenign endometriumMedical recordsRisk factorsMitogenic Insulin Receptor A Increases in the Rodent Pituitary at the Onset of Puberty
SALEH F, TAYLOR H, FLANNERY C. Mitogenic Insulin Receptor A Increases in the Rodent Pituitary at the Onset of Puberty. Diabetes 2018, 67 DOI: 10.2337/db18-245-lb.Peer-Reviewed Original ResearchOnset of pubertyIGF-1RFVB/NJ miceIGF-1R levelsPhysiological insulin resistanceWeek old micePeri-pubertal girlsPituitary hormone productionT-testInitiation of pubertyStudent's t-testSteroid hormone synthesisActive folliculogenesisHPO axisOvarian axisInsulin resistanceRisk factorsReceptor expressionIGF-1Normal insulinOld miceVaginal openingPuberty developmentHormone productionSplice variant isoformsReducing severe hypoglycaemia in hospitalised patients with diabetes: Early outcomes of standardised reporting and management
Araque KA, Kadayakkara DK, Gigauri N, Sheehan D, Majumdar S, Buller G, Flannery CA. Reducing severe hypoglycaemia in hospitalised patients with diabetes: Early outcomes of standardised reporting and management. BMJ Open Quality 2018, 7: e000120. PMID: 29756070, PMCID: PMC5942454, DOI: 10.1136/bmjoq-2017-000120.Peer-Reviewed Original ResearchSystems-based interventionsGeneral medical wardsHypoglycaemic eventsMedian timeHospitalised adultsMedical wardsBasal-bolus insulin regimenRecurrent hypoglycaemic eventsSevere hypoglycaemic eventsFS testingHypoglycemia protocolInsulin regimenSevere hypoglycaemiaAdult patientsCumulative incidenceRecurrent hypoglycemiaSecondary outcomesAcute managementPrimary outcomeProlonged hospitalizationEndocrine consultationPhysician notificationEarly outcomesPoor outcomeMin postinterventionInsulin Regulates Glycogen Synthesis in Human Endometrial Glands Through Increased GYS2
Flannery CA, Choe GH, Cooke KM, Fleming AG, Radford CC, Kodaman PH, Jurczak MJ, Kibbey RG, Taylor HS. Insulin Regulates Glycogen Synthesis in Human Endometrial Glands Through Increased GYS2. The Journal Of Clinical Endocrinology & Metabolism 2018, 103: 2843-2850. PMID: 29726999, PMCID: PMC6276707, DOI: 10.1210/jc.2017-01759.Peer-Reviewed Original ResearchConceptsGlucose metabolismGlycogen synthesisSecretory phase endometriumEndometrial epithelial cellsHuman endometrial glandsGlycogen synthase kinase 3α/βSynthase kinase 3α/βMaternal obesityHealthy womenEndometrial glandsEarly pregnancyHuman endometriumGSK3α/βOutcome measurementsSuccessful implantationFetal developmentEndometriumCritical metabolic functionsInsulinGlycogen contentProgesteroneSustain embryo developmentEpithelial cellsInsulin receptorPotential role
2017
Ovarian Morphology by Transabdominal Ultrasound Correlates With Reproductive and Metabolic Disturbance in Adolescents With PCOS
Rackow BW, Brink H, Hammers L, Flannery CA, Lujan ME, Burgert TS. Ovarian Morphology by Transabdominal Ultrasound Correlates With Reproductive and Metabolic Disturbance in Adolescents With PCOS. Journal Of Adolescent Health 2017, 62: 288-293. PMID: 29217212, PMCID: PMC9843701, DOI: 10.1016/j.jadohealth.2017.09.005.Peer-Reviewed Original ResearchConceptsPolycystic ovary syndromeOvarian volumeOvarian areaOvarian morphologyTotal testosteroneFree testosteroneTransabdominal ultrasonographyFollicle distribution patternBody mass indexRetrospective pilot studyRank correlation coefficientOvary syndromeHormonal testsIndependent predictorsMass indexUltrasound correlatesPhysical examinationFollicle numberMenstrual cycleMetabolic disturbancesHormone ratioMetabolic dysfunctionSonographic featuresReproductive dysfunctionGlucose levelsTime course analysis of RNA quality in placenta preserved by RNAlater or flash freezing
Martin NM, Cooke KM, Radford CC, Perley LE, Silasi M, Flannery CA. Time course analysis of RNA quality in placenta preserved by RNAlater or flash freezing. American Journal Of Reproductive Immunology 2017, 77 PMID: 28138995, PMCID: PMC5397349, DOI: 10.1111/aji.12637.Peer-Reviewed Original Research
2016
Endometrial Cancer-Associated FGF18 Expression Is Reduced by Bazedoxifene in Human Endometrial Stromal Cells In Vitro and in Murine Endometrium
Flannery CA, Fleming AG, Choe GH, Naqvi H, Zhang M, Sharma A, Taylor HS. Endometrial Cancer-Associated FGF18 Expression Is Reduced by Bazedoxifene in Human Endometrial Stromal Cells In Vitro and in Murine Endometrium. Endocrinology 2016, 157: 3699-3708. PMID: 27267714, PMCID: PMC5045514, DOI: 10.1210/en.2016-1233.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnimalsBasic Helix-Loop-Helix Transcription FactorsCarcinoma, EndometrioidCase-Control StudiesCells, CulturedEndometrial HyperplasiaEndometrial NeoplasmsEndometriumFemaleFibroblast Growth FactorsGene Expression ProfilingHumansIndolesMiceMiddle AgedSelective Estrogen Receptor ModulatorsConceptsStromal cellsPostmenopausal womenHormone therapyEpithelial proliferationFGF18 expressionAntiproliferative effectsSelective estrogen receptor modulatorsHuman endometrial stromal cellsGrowth factorBZA/CEMenopausal hormone therapyEndometrial stromal cellsBreast cancer riskEstrogen receptor modulatorsCD1 female miceE74-like factor 5Normal proliferative endometriumParacrine growth factorPrimary stromal cellsTyrosine kinase receptor 2Fibroblast growth factorEndometrial hyperplasiaEndometrial proliferationEndometrial cancerEndometrial adenocarcinomaDifferential Expression of IR-A, IR-B and IGF-1R in Endometrial Physiology and Distinct Signature in Adenocarcinoma
Flannery CA, Saleh FL, Choe GH, Selen DJ, Kodaman PH, Kliman HJ, Wood TL, Taylor HS. Differential Expression of IR-A, IR-B and IGF-1R in Endometrial Physiology and Distinct Signature in Adenocarcinoma. The Journal Of Clinical Endocrinology & Metabolism 2016, 101: 2883-2891. PMID: 27088794, PMCID: PMC4929835, DOI: 10.1210/jc.2016-1795.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAntigens, CDCarcinoma, EndometrioidCells, CulturedEndometrial HyperplasiaEndometrial NeoplasmsEndometriumFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMenstrual CycleMiddle AgedProtein SubunitsReceptor, IGF Type 1Receptor, InsulinTranscriptomeConceptsIGF-1R expressionEndometrial hyperplasiaNormal endometriumEndometrial physiologySecretory phaseProliferative phaseIGF-1 receptor mRNAIR-B expressionNormal secretory phaseType 2 diabetesSex steroid treatmentEarly secretory phaseEarly proliferative phaseNormal proliferative phaseEndometrial proliferationEndometrioid adenocarcinomaComplex hyperplasiaEndometrial adenocarcinomaMass indexMenstrual cycleRisk factorsReceptor expressionIGF-1RMAIN OUTCOMEReceptor mRNADevelopment of a Quantitative PCR Assay for Detection of Human Insulin-Like Growth Factor Receptor and Insulin Receptor Isoforms
Flannery CA, Rowzee AM, Choe GH, Saleh FL, Radford CC, Taylor HS, Wood TL. Development of a Quantitative PCR Assay for Detection of Human Insulin-Like Growth Factor Receptor and Insulin Receptor Isoforms. Endocrinology 2016, 157: 1702-1708. PMID: 26862994, PMCID: PMC4816738, DOI: 10.1210/en.2015-1698.Peer-Reviewed Original ResearchConceptsSplice variantsInsulin-like growth factor (IGF) ligandsInsulin-like growth factor receptorGrowth factor ligandsSpecific molecular signaturesQuantitative PCR assaysGrowth factor receptorHigh homologyMRNA sequencesQuantitative RT-PCRIGF-1 receptorFactor ligandInsulin receptor isoformsCompetition assaysPrimer pairsRelative abundanceInsulin receptorMolecular signaturesCell typesDifferent tissuesIGF-1R mRNAFactor receptorExpression levelsGel electrophoresisReceptor isoforms
2015
H19 lncRNA alters stromal cell growth via IGF signaling in the endometrium of women with endometriosis
Ghazal S, McKinnon B, Zhou J, Mueller M, Men Y, Yang L, Mueller M, Flannery C, Huang Y, Taylor HS. H19 lncRNA alters stromal cell growth via IGF signaling in the endometrium of women with endometriosis. EMBO Molecular Medicine 2015, 7: 996-1003. PMID: 26089099, PMCID: PMC4551339, DOI: 10.15252/emmm.201505245.Peer-Reviewed Original ResearchConceptsChronic pelvic painReproductive-aged womenEndometrium of womenEndometrial stromal cellsStromal cell growthEndometrial preparationPelvic painEutopic endometriumAged womenEndometriosisNormal controlsStromal cellsH19 expressionImpact fertilityMolecular spongeH19/letNovel therapeuticsReduced proliferationInfertilityWomenEndometriumTurn inhibitsMicroRNA let-7Molecular mechanismsCell growth
2014
mRNA-Binding Protein TIA-1 Reduces Cytokine Expression in Human Endometrial Stromal Cells and Is Down-Regulated in Ectopic Endometrium
Karalok HM, Aydin E, Saglam O, Torun A, Guzeloglu-Kayisli O, Lalioti MD, Kristiansson H, Duke CM, Choe G, Flannery C, Kallen CB, Seli E. mRNA-Binding Protein TIA-1 Reduces Cytokine Expression in Human Endometrial Stromal Cells and Is Down-Regulated in Ectopic Endometrium. The Journal Of Clinical Endocrinology & Metabolism 2014, 99: e2610-e2619. PMID: 25140393, PMCID: PMC4255110, DOI: 10.1210/jc.2013-3488.Peer-Reviewed Original ResearchConceptsHuman endometrial stromal cellsTNF-α expressionTIA-1 expressionEndometrial stromal cellsIL-6Pathogenesis of endometriosisMenstrual cycleTIA-1Endometrial tissueEctopic endometriumImmune factorsHistological scoresCultured human endometrial stromal cellsSteroid hormonesStromal cellsGrowth factorElevated IL-6Ectopic endometrial tissueNormal menstrual cycleEutopic endometrial tissuesGrowth factor expressionT-cell intracellular antigenEndometrial cytokinesEndometrial functionControl womenThe H19/let-7 double-negative feedback loop contributes to glucose metabolism in muscle cells
Gao Y, Wu F, Zhou J, Yan L, Jurczak MJ, Lee HY, Yang L, Mueller M, Zhou XB, Dandolo L, Szendroedi J, Roden M, Flannery C, Taylor H, Carmichael GG, Shulman GI, Huang Y. The H19/let-7 double-negative feedback loop contributes to glucose metabolism in muscle cells. Nucleic Acids Research 2014, 42: 13799-13811. PMID: 25399420, PMCID: PMC4267628, DOI: 10.1093/nar/gku1160.Peer-Reviewed Original ResearchConceptsDouble-negative feedback loopLet-7PI3K/Akt-dependent phosphorylationLet-7 targetsHuman genetic disordersAkt-dependent phosphorylationMuscle cellsInsulin-resistant rodentsSponge lncRNAsMolecular spongeH19 lncRNAFeedback loopGrowth controlDepletion resultsH19Impaired insulinLncRNAsTarget miRNAGlucose uptakeGenetic disordersBiogenesisCellsKSRPPhosphorylationMicroRNAsGlucose and Metformin Modulate Human First Trimester Trophoblast Function: a Model and Potential Therapy for Diabetes‐Associated Uteroplacental Insufficiency
Han CS, Herrin MA, Pitruzzello MC, Mulla MJ, Werner EF, Pettker CM, Flannery CA, Abrahams VM. Glucose and Metformin Modulate Human First Trimester Trophoblast Function: a Model and Potential Therapy for Diabetes‐Associated Uteroplacental Insufficiency. American Journal Of Reproductive Immunology 2014, 73: 362-371. PMID: 25394884, PMCID: PMC4356646, DOI: 10.1111/aji.12339.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis Inducing AgentsAntigens, CDCarrier ProteinsCell LineCell MovementChemokine CCL5Chemokine CXCL1Diabetes ComplicationsDiabetes MellitusEndoglinFemaleGlucoseGranulocyte Colony-Stimulating FactorHumansInflammationInterleukinsMetforminNLR Family, Pyrin Domain-Containing 3 ProteinPlacentaPre-EclampsiaPregnancyPregnancy Trimester, FirstReceptors, Cell SurfaceTrophoblastsUterusVascular Endothelial Growth Factor Receptor-1ConceptsHuman first trimester trophoblast cell lineAnti-angiogenic factor sFlt-1First trimester trophoblast cell lineNalp3/ASC inflammasomeInflammatory cytokines/chemokinesFirst trimester trophoblast cellsGlucose-induced inflammationRisk of preeclampsiaCytokines/chemokinesAbsence of metforminIL-1β productionIL-1β secretionTrophoblast cell lineUteroplacental insufficiencyIL-1βIL-6SFlt-1Trophoblast functionsIL-8Pathogenic roleInflammatory responseASC inflammasomeSupernatant cytokinesPotential therapyExcess glucose