{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:17:11Z","timestamp":1791908231952,"version":"4.3.4"},"reference-count":40,"publisher":"The Endocrine Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Context:<\/jats:title><jats:p>Hyperandrogenism and oxidative stress are related in polycystic ovary syndrome (PCOS), but it is unknown whether hyperandrogenemia can activate oxidative stress.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective:<\/jats:title><jats:p>The purpose of this study was to determine the effect of oral androgen administration on fasting and glucose-stimulated leukocytic reactive oxygen species (ROS) generation, reduced nicotinamide adenine dinucleotide phosphate oxidase p47phox subunit gene expression, and plasma thiobarbituric acid-reactive substances (TBARS) in lean healthy reproductive-age women.<\/jats:p><\/jats:sec><jats:sec><jats:title>Participants, Design, and Setting:<\/jats:title><jats:p>Sixteen lean healthy ovulatory reproductive-age women were treated with 130 mg dehydroepiandrosterone (DHEA) or placebo (n = 8 each) for 5 d in this randomized, controlled, double-blind study that was performed at an an academic medical center.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Outcome Measures:<\/jats:title><jats:p>Leukocytic ROS generation, p47phox gene expression, and plasma TBARS were quantified in the fasting state and 2 h after glucose ingestion, before and after treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>Before treatment, subjects receiving DHEA or placebo exhibited no differences in androgens or any prooxidant markers while fasting and after glucose ingestion. Compared with placebo, DHEA administration raised levels of testosterone, androstenedione, and DHEA-sulfate, increased the percent change in glucose-challenged p47phox RNA content, and increased the percent change in fasting and glucose-challenged ROS generation from mononuclear cells and polymorphonuclear cells, p47phox protein content, and plasma TBARS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion:<\/jats:title><jats:p>Elevation of circulating androgens comparable to what is present in PCOS increases leukocytic ROS generation, p47phox gene expression, and plasma TBARS to promote oxidative stress in lean healthy reproductive-age women. Thus, hyperandrogenemia activates and sensitizes leukocytes to glucose in this population.<\/jats:p><\/jats:sec>","DOI":"10.1210\/jc.2012-1259","type":"journal-article","created":{"date-parts":[[2012,5,9]],"date-time":"2012-05-09T03:09:31Z","timestamp":1336532971000},"page":"2836-2843","source":"Crossref","is-referenced-by-count":62,"title":["Hyperandrogenism Sensitizes Leukocytes to Hyperglycemia to Promote Oxidative Stress in Lean Reproductive-Age Women"],"prefix":"10.1210","volume":"97","author":[{"given":"Frank","family":"Gonz\u00e1lez","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology (F.G.), Indiana University School of Medicine, Indianapolis, Indiana 46202"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. Sreekumaran","family":"Nair","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (K.S.N., J.M.S.), Rochester, Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice K.","family":"Daniels","sequence":"additional","affiliation":[{"name":"Endocrine Research Unit, and Departments Obstetrics and Gynecology (J.K.D., E.B.), Rochester, Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eati","family":"Basal","sequence":"additional","affiliation":[{"name":"Endocrine Research Unit, and Departments Obstetrics and Gynecology (J.K.D., E.B.), Rochester, Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill M.","family":"Schimke","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (K.S.N., J.M.S.), Rochester, Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilary E.","family":"Blair","sequence":"additional","affiliation":[{"name":"Laboratory Medicine and Pathology (H.E.B.), College of Medicine, Mayo Clinic, Rochester, Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071615365724000_B1","first-page":"3078","article-title":"Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern Unites States: a prospective study.","volume":"83","author":"Knochenhauer","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615365724000_B2","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1210\/jc.2005-1457","article-title":"Relative prevalence of different androgen excess disorders in 950 women refereed because of clinical hyperandrogenism.","volume":"91","author":"Carmina","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615365724000_B3","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1210\/jcem-50-1-113","article-title":"Correlation of hyperandrogenism with hyperinsulinemia in polycystic ovarian disease.","volume":"50","author":"Burghen","year":"1980","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615365724000_B4","first-page":"2001","article-title":"Insulin stimulates testosterone biosynthesis by human theca cells from women with polycystic ovary syndrome by activating its own receptor and using inositoglycan mediators as the signal transduction system.","volume":"83","author":"Nestler","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615365724000_B5","doi-asserted-by":"crossref","first-page":"24519","DOI":"10.1016\/S0021-9258(17)31418-7","article-title":"The respiratory burst oxidase.","volume":"269","author":"Chanock","year":"1994","journal-title":"J Biol Chem"},{"key":"2020071615365724000_B6","first-page":"356A","article-title":"Understanding activation of NADPH oxidase: a structural characterization of p47phox.","volume":"84","author":"Groemping","year":"2003","journal-title":"Biophys J"},{"key":"2020071615365724000_B7","doi-asserted-by":"crossref","first-page":"21340","DOI":"10.1016\/S0021-9258(19)30085-7","article-title":"Hyperglycemia can cause membrane lipid peroxidation and osmotic fragility in human red blood cells.","volume":"264","author":"Jain","year":"1989","journal-title":"J Biol Chem"},{"key":"2020071615365724000_B8","first-page":"113A","article-title":"Increased carbonylation of proteins in diabetes.","volume":"44","author":"Aljada","year":"1995","journal-title":"Diabetes"},{"key":"2020071615365724000_B9","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/S0140-6736(96)90013-6","article-title":"Oxidative damage to DNA in diabetes mellitus.","volume":"347","author":"Dandona","year":"1996","journal-title":"Lancet"},{"key":"2020071615365724000_B10","doi-asserted-by":"crossref","first-page":"4854","DOI":"10.1073\/pnas.91.11.4854","article-title":"Tumor necrosis factor \u03b1 inhibits signaling from the insulin receptor.","volume":"91","author":"Hotamisligil","year":"1994","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071615365724000_B11","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1210\/jc.2005-1696","article-title":"Reactive oxygen species-induced oxidative stress in the development of insulin resistance and hyperandrogenism in polycystic ovary syndrome.","volume":"91","author":"Gonz\u00e1lez","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615365724000_B12","doi-asserted-by":"crossref","first-page":"5336","DOI":"10.1210\/jc.2005-0694","article-title":"Hyperglycemia alters tumor necrosis factor-\u03b1 release from mononuclear cells in women with polycystic ovary syndrome.","volume":"90","author":"Gonz\u00e1lez","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615365724000_B13","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1161\/ATVBAHA.111.229260","article-title":"Oxidized low-density lipoprotein activates p66Shc via lectin-like oxidized low-density lipoprotein receptor-1, protein kinase C-\u03b2, and c-Jun N-terminal kinase kinase in human endothelial cells.","volume":"31","author":"Shi","year":"2011","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2020071615365724000_B14","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1046\/j.1471-4159.1998.70010268.x","article-title":"Increased protein oxidation in human substantia nigra pars compacta in comparison with basal ganglia and prefrontal cortex measured with an improved dinitrophenylhydrazine assay.","volume":"70","author":"Floor","year":"1998","journal-title":"J Neurochem"},{"key":"2020071615365724000_B15","article-title":"Lipid-peroxidation and peroxiredoxin-overoxidation in the erythrocytes of non-insulin-dependent type 2 diabetic men during acute exercise","author":"Brinkmann","year":"2011","journal-title":"Eur J Appl Physiol"},{"key":"2020071615365724000_B16","doi-asserted-by":"crossref","first-page":"3505","DOI":"10.1210\/jc.2009-0466","article-title":"Mitochondrial complex I impairment in leukocytes from polycystic ovary syndrome patients with insulin resistance.","volume":"94","author":"Victor","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615365724000_B17","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1111\/j.1399-5618.2005.00201.x","article-title":"Reproductive function and risk for PCOS in women treated for bipolar disorder.","volume":"7","author":"Rasgon","year":"2005","journal-title":"Bipolar Disord"},{"key":"2020071615365724000_B18","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1530\/EJE-11-0840","article-title":"Inosotol administration reduces oxidative stress in erythrocytes of patients with polycystic ovary syndrome.","volume":"166","author":"Don\u00e0","year":"2012","journal-title":"Eur J Endocrinol"},{"key":"2020071615365724000_B19","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1161\/01.ATV.15.5.562","article-title":"Effects of androgens on coronary artery atherosclerosis and atherosclerosis-related impairment of vascular responsiveness.","volume":"15","author":"Adams","year":"1995","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2020071615365724000_B20","first-page":"215A","article-title":"Hyperandrogenism is related to reactive oxygen species generation from pre-activated leukocytes in polycystic ovary syndrome.","volume":"14","author":"Gonz\u00e1lez","year":"2007","journal-title":"Reprod Sci"},{"key":"2020071615365724000_B21","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1677\/joe.1.06579","article-title":"In vitro evidence that hyperglycemia stimulates tumor necrosis factor-\u03b1 release in obese women with polycystic ovary syndrome.","volume":"188","author":"Gonz\u00e1lez","year":"2006","journal-title":"J Endocrinol"},{"key":"2020071615365724000_B22","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1210\/jc.2005-2327","article-title":"Increased activation of nuclear factor \u03baB triggers inflammation and insulin resistance in polycystic ovary syndrome.","volume":"91","author":"Gonz\u00e1lez","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615365724000_B23","doi-asserted-by":"crossref","first-page":"E297","DOI":"10.1152\/ajpendo.00416.2011","article-title":"Hyperandrogenism sensitizes mononuclear cells to promote glucose-induced inflammation in lean reproductive-age women.","volume":"302","author":"Gonz\u00e1lez","year":"2012","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2020071615365724000_B24","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.2337\/diacare.22.9.1462","article-title":"Insulin sensitivity indices obtained from oral glucose tolerance testing.","volume":"22","author":"Matsuda","year":"1999","journal-title":"Diabetes Care"},{"key":"2020071615365724000_B25","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.1038\/oby.2007.289","article-title":"Obese reproductive age women exhibit a proatherogenic inflammatory response during hyperglycemia.","volume":"15","author":"Gonz\u00e1lez","year":"2007","journal-title":"Obesity"},{"key":"2020071615365724000_B26","doi-asserted-by":"crossref","first-page":"E203","DOI":"10.1152\/ajpendo.2001.280.2.E203","article-title":"Age effect on transcript levels and synthesis rate of muscle MHC and response to resistance exercise.","volume":"80","author":"Balagopal","year":"2001","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2020071615365724000_B27","first-page":"99","article-title":"Translocation of p47phox and activation of NADPH oxidase in mononuclear cells.","volume":"196","author":"Aljada","year":"2002","journal-title":"Methods Mol Biol"},{"key":"2020071615365724000_B28","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.metabol.2005.08.022","article-title":"Altered tumor necrosis factor-\u03b1 release from mononuclear cells of obese reproductive age women during hyperglycemia.","volume":"55","author":"Gonz\u00e1lez","year":"2006","journal-title":"Metabolism"},{"key":"2020071615365724000_B29","doi-asserted-by":"crossref","first-page":"35279","DOI":"10.1074\/jbc.M706762200","article-title":"A Subpopulation of macrophages infiltrates hypertrophic adipose tissue and is activated by free fatty acids via toll-like receptors 2 and 4 and JNK-dependent pathways.","volume":"282","author":"Nguyen","year":"2007","journal-title":"J Biol Chem"},{"key":"2020071615365724000_B30","doi-asserted-by":"crossref","first-page":"E1300","DOI":"10.1152\/ajpendo.90885.2008","article-title":"Muscle inflammatory response and insulin resistance: synergistic interaction between macrophages and fatty acids leads to impaired insulin action.","volume":"296","author":"Varma","year":"2009","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2020071615365724000_B31","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1172\/JCI200319246","article-title":"Obesity is associated with macrophage accumulation in adipose tissue.","volume":"112","author":"Weisberg","year":"2003","journal-title":"J Clin Invest"},{"key":"2020071615365724000_B32","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.cmet.2008.08.015","article-title":"Ablation of CD11c-positive cells normalize insulin sensitivity in obese insulin resistant animals.","volume":"8","author":"Patsouris","year":"2008","journal-title":"Cell Metab"},{"key":"2020071615365724000_B33","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1161\/01.CIR.0000142055.53122.FA","article-title":"Circulating mononuclear cells in the obese are in a proinflammatory state.","volume":"110","author":"Ghanim","year":"2004","journal-title":"Circulation"},{"key":"2020071615365724000_B34","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1172\/JCI0215704","article-title":"Androgen receptor-mediated inhibition of cutaneous wound healing.","volume":"110","author":"Ashcroft","year":"2002","journal-title":"J Clin Invest"},{"key":"2020071615365724000_B35","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1093\/jnci\/91.14.1227","article-title":"Effects of antioxidants on androgen-induced AP-1 and NF-\u03baB DNA-binding activity in prostate carcinoma cells.","volume":"91","author":"Ripple","year":"1999","journal-title":"J Natl Cancer Inst"},{"key":"2020071615365724000_B36","doi-asserted-by":"crossref","first-page":"e11302","DOI":"10.1371\/journal.pone.0011302","article-title":"Androgen excess produces systemic oxidative stress and predisposes to \u03b2-cell failure in female mice.","volume":"5","author":"Liu","year":"2010","journal-title":"PLoS one"},{"key":"2020071615365724000_B37","doi-asserted-by":"crossref","first-page":"2500","DOI":"10.1210\/jc.2006-2725","article-title":"Abdominal fat quantity and distribution in women with polycystic ovary syndrome and extent of its relation to insulin resistance.","volume":"92","author":"Carmina","year":"2007","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615365724000_B38","doi-asserted-by":"crossref","first-page":"3249","DOI":"10.1210\/endo.139.7.6118","article-title":"Dehydroepiandrosterone decreases tumor necrosis factor-\u03b1 and restores insulin sensitivity: independent effect from secondary weight reduction in genetically obese zucker fatty rats.","volume":"139","author":"Kimura","year":"1998","journal-title":"Endocrinology"},{"key":"2020071615365724000_B39","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.2337\/diabetes.48.8.1579","article-title":"Dehydroepiandrosterone suppresses the elevated hepatic glucose-6-phospatase and fructose-1,6-biphosphatase activities in C57BL\/Ksj-db\/db mice.","volume":"48","author":"Aoki","year":"1999","journal-title":"Diabetes"},{"key":"2020071615365724000_B40","doi-asserted-by":"crossref","first-page":"R114","DOI":"10.1186\/cc7963","article-title":"DHEA-dependent and organ-specific regulation of TNF-\u03b1 mRNA expression in a murine polymicrobial sepsis and trauma model.","volume":"13","author":"Barkhausen","year":"2009","journal-title":"Critical Care"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/97\/8\/2836\/9042051\/jcem2836.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/97\/8\/2836\/9042051\/jcem2836.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,15]],"date-time":"2022-01-15T06:02:01Z","timestamp":1642226521000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/97\/8\/2836\/2823403"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,8,1]]},"references-count":40,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2012,8,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2012-1259","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,8,1]]}}}