Catecholamines in stress: molecular mechanisms of gene expression.
The catecholamines play key roles in orchestrating the response to stress. While this is crucial to handle emergency situations, stress becomes maladaptive when prolonged or repeated, increasing allosteric load and susceptibility to a wide range of serious diseases. The time frame of the regulation of gene expression, especially as it relates to catecholamine (CA) biosynthetic enzymes are compared in three crucial catecholaminergic locations, the adrenal medulla, sympathetic ganglia and locus coeruleus in male animals. The adrenal medulla displays very rapid response to stress and gene profiling reveals a wide repertoire of target genes, many of them activated by single and not by repeated stress. In contrast to the adrenal medulla, the sympathetic ganglia are especially responsive to activation of the HPA axis, and ACTH may have a direct effect. The locus coeruleus, origin of most of the noradrenergic neurons innervating much of the brain, displays activation of additional signalling pathways and transcription factor with repeated compared to single exposure to stress. Most of the studies have been performed in males. However, there is considerable evidence that females respond differently to stress. Estradiol can regulate TH, DBH and GTPCH gene expression, as well as to modulate its response to other second messenger such as cAMP. Prior treatment with estradiol was found to alter the response of CA biosynthetic enzymes to stress. This emphasizes the tissue and sex specific features of the mechanistic underpinning of the adaptation or maladaptation of the catecholaminergic systems to stress and provides the basis for specific interventions. Key words: Adrenal medulla - Catecholamine biosynthesis - Estrogen - Sympathetic ganglia - Locus coeruleus - Stress - Transcription factors.
Sabban
Esther L
EL
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA. sabban@nymc.edu
D000313:Adrenal Medulla / Q000502:physiology; D000818:Animals; D002395:Catecholamines / Q000096:biosynthesis / Q000502:physiology*; D004967:Estrogens / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007103:Immobilization / Q000502:physiology; D008125:Locus Coeruleus / Q000502:physiology; D008297:Male; D013312:Stress, Physiological / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000502:physiology
D002395:Catecholamines; D004967:Estrogens