Induction of tyrosine hydroxylase gene expression by glucocorticoids in the perinatal rat brain is age-dependent.
Brain noradrenergic system has been implicated in early-life stress effects on adult physiology and behavior; however, the mechanisms for this relationship are not clear. Here we tested the hypothesis that stress hormones, glucocorticoids, may affect noradrenergic system activity by modulating gene expression and function of tyrosine hydroxylase (TH), the key enzyme for catecholamine synthesis, in the rat brain during perinatal life. We have shown that TH mRNA levels and enzyme activity increase in the fetal rat brainstem during the last days of pregnancy. Administration of hydrocortisone or dexamethasone to female rats on day 20 of pregnancy significantly increased TH mRNA levels (real-time PCR) and enzyme activity (DOPA accumulation after inhibition of aromatic L: -amino acid decarboxylase with NSD-1015) as well as noradrenaline concentrations in the brainstem of fetuses 6 h after the treatment. Similar glucocorticoid effects on fetal TH and noradrenaline were observed 72 h after the treatment with hydrocortisone on days 16 and 18 of pregnancy. In contrast to fetuses, no effects on the TH were revealed in the brainstem of neonatal pups after single or repeated injections of hydrocortisone or dexamethasone. TH gene expression remains at a relatively constant level in the early neonatal rat brain. The results suggest that glucocorticoids are capable of inducing TH at both transcriptional and enzyme activity levels in the brainstem of near-term fetuses.
Functional Neurogenomics Laboratory, Institute of Cytology and Genetics, Lavrentjev Av., 10, 630090 Novosibirsk, Russia. kalin@bionet.nsc.ru
Tatyana S
TS
Kalinina
Galina T
GT
Shishkina
Nikolay N
NN
Dygalo
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000201:enzymology*; D001933:Brain Stem / Q000187:drug effects / Q000201:enzymology; D004790:Enzyme Induction / Q000502:physiology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005938:Glucocorticoids / Q000502:physiology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis* / Q000235:genetics*
D005938:Glucocorticoids; D012333:RNA, Messenger; D014446:Tyrosine 3-Monooxygenase