Molecular regulation of gene expression of catecholamine biosynthetic enzymes by stress: sympathetic ganglia versus adrenal medulla.
Stress induces tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) gene expression in sympathetic ganglia and adrenal medulla (AM). However, distinct molecular mechanisms appear to regulate these genes in these locations. The elevation of TH mRNA in response to single immobilization stress (IMO) in AM is robust, but transient, while the induction of TH and DBH mRNAs in sympathetic ganglia is slower and more long lasting. Injections of adrenocorticotropic hormone (ACTH) elicited induction of TH and DBH gene expression in rat sympathetic ganglia, but not in AM. The superior cervical (SCG) and stellate (StG) ganglia, but not AM, were found to express mRNA for the MC-2 receptor, the major ACTH responsive receptor in adrenal cortex. IMO led to increase in MC-2 receptor mRNA levels in SCG. Thus, ACTH, via the MC-2 receptor, may be directly involved in the stress-elicited regulation of norepinephrine biosynthesis in sympathetic ganglia. The signaling pathways triggered by IMO differed in these locations. In AM, IMO triggered activation of the MAP kinase, JNK, and induction of AP1 factors, Egr1 and phosphorylation of CREB. In contrast in the SCG, with IMO we did not observe changes in JNK and little binding to the AP1 motif of the TH promoter. However, there was an increase in CREB binding to the CRE site of the TH promoter. The results reveal differential mechanisms of regulation of catecholamine biosynthetic enzymes by stress in two components of the sympathoadrenal system and should provide basis for possible selective pharmacologic interventions.
Sabban
Esther L
EL
Department of Biochemistry and Molecular Biology, Basic Sciences Building, New York Medical College, Valhalla, NY 10595, USA. Sabban@nymc.edu
Nankova
Bistra B
BB
Serova
Lidia I
LI
Kvetnansky
Richard
R
Liu
Xiaoping
X
D000313:Adrenal Medulla / Q000201:enzymology*; D000818:Animals; D002395:Catecholamines / Q000096:biosynthesis*; D004299:Dopamine beta-Hydroxylase / Q000235:genetics*; D005728:Ganglia, Sympathetic / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000201:enzymology*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
D002395:Catecholamines; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase