Regulation of gene expression of catecholamine biosynthetic enzymes in dopamine-beta-hydroxylase- and CRH-knockout mice exposed to stress.
Norepinephrine-deficient mice harbor a disruption of the gene for dopamine-beta-hydroxylase (DBH-KO). Corticotropin-releasing hormone knockout mice (CRH-KO) have markedly reduced HPA activity. The aim of the present work was to study how deficiency of DBH and CRH would affect tyrosine hydroxylase (TH), DBH, and phenylethanolamine N-methyltransferase (PNMT) gene expression and protein levels in the adrenal medulla (AM) and stellate ganglia (SG) of control and stressed mice. Both in AM and SG, single immobilization significantly increased TH and DBH mRNA and protein levels both in wild-type (WT) and CRH-KO mice. On the other hand, the stress-triggered increase in PNMT mRNA and protein levels seen in WT mice was absent in CRH-KO mice. DBH-KO mice are more sensitive to stress but survive a single 2 h restraint stress in a tube. The increase in TH mRNA levels induced by restraint stress in WT was not observed in DBH-KO mice. PNMT mRNA and especially PNMT protein levels were significantly elevated in AM of DBH-KO mice. In SG of DBH-KO mice, TH mRNA levels were not affected; however, PNMT gene expression was highly elevated. Thus, disruption of the DBH gene surprisingly blocks the stress-induced elevation of TH mRNA levels in AM but increases PNMT gene expression in both AM and SG. Our data indicate that adrenergic signaling is required for stress-induced increase in TH mRNA and that this signaling restrains stress-induced increase in PNMT mRNA. They also confirm that the HPA system plays a crucial role in the stress-induced regulation of PNMT gene expression.
Kvetnanský
Richard
R
Institute of Experimental Endocrinology, Centre of Excellence CENDO, Slovak Academy of Sciences, Bratislava, Slovak Republic. ueenkvet@savba.sk
Krizanova
Olga
O
Tillinger
Andrej
A
Sabban
Esther L
EL
Thomas
Steven A
SA
Kubovcakova
Lucia
L
D000313:Adrenal Medulla / Q000502:physiology; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D004299:Dopamine beta-Hydroxylase / Q000235:genetics / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010625:Phenylethanolamine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D012149:Restraint, Physical; D015398:Signal Transduction / Q000502:physiology; D013233:Stellate Ganglion / Q000502:physiology; D013315:Stress, Psychological; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
D002395:Catecholamines; D003346:Corticotropin-Releasing Hormone; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D010625:Phenylethanolamine N-Methyltransferase