{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:08:21Z","timestamp":1791461301638,"version":"4.3.4"},"reference-count":78,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,6,2]],"date-time":"2014-06-02T00:00:00Z","timestamp":1401667200000},"content-version":"vor","delay-in-days":32,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:p>The stress system effectively restores the internal balance\u2014or homeostasis\u2014of living organisms in the face of random external or internal changes, the stressors. This highly complex system helps organisms to provide a series of neuroendocrine responses to stressors\u2014the stress response\u2014through coordinated activation of the hypothalamic\u2013pituitary\u2013adrenal (HPA) axis and the locus coeruleus\/norepinephrine autonomic nervous systems. In addition to stressors, life is influenced by daily light\/dark changes due to the 24\u2010h rotation of Earth. To adjust to these recurrent day\/night cycles, the biological clock system employs the heterodimer of transcription factors circadian locomotor output cycle kaput\/brain\u2013muscle\u2013arnt\u2013like protein 1 (CLOCK\/BMAL1), along with a set of other transcription factors, to regulate the circadian pattern of gene expression. Interestingly, the stress system, through the HPA axis, communicates with the clock system; therefore, any uncoupling or dysregulation could potentially cause several disorders, such as metabolic, autoimmune, and mood disorders. In this review, we discuss the biological function of the two systems, their interactions, and the clinical implications of their dysregulation or uncoupling.<\/jats:p>","DOI":"10.1111\/nyas.12464","type":"journal-article","created":{"date-parts":[[2014,6,2]],"date-time":"2014-06-02T20:00:05Z","timestamp":1401739205000},"page":"71-80","source":"Crossref","is-referenced-by-count":165,"title":["Circadian endocrine rhythms: the hypothalamic\u2013pituitary\u2013adrenal axis and its actions"],"prefix":"10.1111","volume":"1318","author":[{"given":"Nicolas C.","family":"Nicolaides","sequence":"first","affiliation":[{"name":"Division of Endocrinology Metabolism, and Diabetes, First Department of Pediatrics, University of Athens Medical School, \u201cAghia Sophia\u201d Children's Hospital  Athens Greece"},{"name":"Division of Endocrinology and Metabolism Clinical Research Center, Biomedical Research Foundation of the Academy of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelia","family":"Charmandari","sequence":"additional","affiliation":[{"name":"Division of Endocrinology Metabolism, and Diabetes, First Department of Pediatrics, University of Athens Medical School, \u201cAghia Sophia\u201d Children's Hospital  Athens Greece"},{"name":"Division of Endocrinology and Metabolism Clinical Research Center, Biomedical Research Foundation of the Academy of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George P.","family":"Chrousos","sequence":"additional","affiliation":[{"name":"Division of Endocrinology Metabolism, and Diabetes, First Department of Pediatrics, University of Athens Medical School, \u201cAghia Sophia\u201d Children's Hospital  Athens Greece"},{"name":"Division of Endocrinology and Metabolism Clinical Research Center, Biomedical Research Foundation of the Academy of Athens  Athens Greece"},{"name":"Saudi Diabetes Study Research Group King Fahd Medical Research Center King Abdulaziz University  Jeddah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoshige","family":"Kino","sequence":"additional","affiliation":[{"name":"Program in Reproductive and Adult Endocrinology <i>Eunice Kennedy Shriver<\/i> National Institute of Child Health and Human Development, National Institutes of Health  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,6,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199505183322008"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0278-5846(85)90187-3"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4899-2064-5_13"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1159\/000181089"},{"key":"e_1_2_9_6_1","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1210\/jcem.84.5.5631","article-title":"Clinical review 104: adrenocorticotropin (ACTH)\u2010 and non\u2010ACTH\u2010mediated regulation of the adrenal cortex: neural and immune inputs","volume":"84","author":"Bornstein S.R.","year":"1999","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-032026"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2004.05.006"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.01-0245com"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/stke.3042005pe48"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra050541"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2009.09.002"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2005.02.006"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2006.09.009"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1042\/bse0400137"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117943"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2004-0112"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.12.4319-4330.2003"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-009-0098-z"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2005.03.025"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.08-117697"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2430"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl207"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1677\/JOE-07-0378"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/35036078"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2009.12.011"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1177\/0748730406293854"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.5.8.2684"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0601416103"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1221592"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1738"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.03.033"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2013.12.013"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0025612"},{"key":"e_1_2_9_35_1","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1159\/000321232","article-title":"Circadian CLOCK\u2010mediated regulation of target\u2010tissue sensitivity to glucocorticoids: implications for cardiometabolic diseases","volume":"20","author":"Kino T.","year":"2011","journal-title":"Endocr. Dev."},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2010.12.001"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2011.08.010"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2011.06.042"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-59427-3.00030-7"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2011.07.003"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2010.09.001"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1677\/JOE-08-0415"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00042.2003"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2005.09.009"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2006.07.002"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0806962106"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.06.050"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10700"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.289.5488.2344"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M509600200"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909733106"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.03.027"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.141.10.3799"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.183500"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.24.7128"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0020377"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1108750"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/87.6.1606"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0803778"},{"key":"e_1_2_9_60_1","first-page":"295","volume-title":"Handbook on Stress and the Brain","author":"Kino T.","year":"2005"},{"key":"e_1_2_9_61_1","first-page":"609","volume-title":"Endocrinology and Metabolism","author":"Chrousos G.P.","year":"2001"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwj185"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2007.01766.x"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1177\/000331979604701109"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0808180106"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22368"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.091283"},{"key":"e_1_2_9_68_1","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1210\/jcem.82.4.3852","article-title":"Circadian relationships between interleukin (IL)\u20106 and hypothalamicpituitary\u2010adrenal axis hormones: failure of IL\u20106 to cause sustained hypercortisolism in patients with early untreated rheumatoid arthritis","volume":"82","author":"Crofford L.J.","year":"1997","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1097\/00043764-200211000-00005"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22597"},{"key":"e_1_2_9_71_1","first-page":"31","article-title":"Shift work and autoimmune thyroid disorders","volume":"19","author":"Magrini A.","year":"2006","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60132-4"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.56.1.27"},{"key":"e_1_2_9_74_1","first-page":"S32","article-title":"Glucocorticoid receptor: implications for rheumatic diseases","volume":"29","author":"Kino T.","year":"2011","journal-title":"Clin. Exp. Rheumatol."},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1670"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11673"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.07.032"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M707114200"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050466"}],"container-title":["Annals of the New York Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fnyas.12464","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nyas.12464","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T22:09:06Z","timestamp":1696284546000},"score":1,"resource":{"primary":{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/10.1111\/nyas.12464"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,5]]},"references-count":78,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2014,5]]}},"alternative-id":["10.1111\/nyas.12464"],"URL":"https:\/\/doi.org\/10.1111\/nyas.12464","archive":["Portico"],"relation":{},"ISSN":["0077-8923","1749-6632"],"issn-type":[{"value":"0077-8923","type":"print"},{"value":"1749-6632","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,5]]}}}