title: Circadian endocrine rhythms: the hypothalamic-pituitary-adrenal axis and its actions.
abstract: The stress system effectively restores the internal balance--or homeostasis--of 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--the stress response--through coordinated activation of the hypothalamic-pituitary-adrenal (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-h 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-muscle-arnt-like 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.
authors.affiliation: Division of Endocrinology, Metabolism, and Diabetes, First Department of Pediatrics, University of Athens Medical School, "Aghia Sophia" Children's Hospital, Athens, Greece; Division of Endocrinology and Metabolism, Clinical Research Center, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
authors.forename: Nicolas C
authors.initials: NC
authors.lastname: Nicolaides
authors.forename: Evangelia
authors.initials: E
authors.lastname: Charmandari
authors.forename: George P
authors.initials: GP
authors.lastname: Chrousos
authors.forename: Tomoshige
authors.initials: T
authors.lastname: Kino
mesh_terms: D056930:ARNTL Transcription Factors / Q000378:metabolism; D000818:Animals; D056926:CLOCK Proteins / Q000378:metabolism; D002940:Circadian Rhythm; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000502:physiology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D010913:Pituitary-Adrenal System / Q000502:physiology*; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism
chemical_list: D056930:ARNTL Transcription Factors; C538960:BMAL1 protein, human; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D056926:CLOCK Proteins; C538943:CLOCK protein, human
keywords: HPA axis; acetylation; circadian clock system; glucocorticoid receptor; glucocorticoids