Tyrosine hydroxylase in the brain and its regulation by glucocorticoids

E. V. Sukhareva, T. S. Kalinina, V. V. Bulygina, N. N. Dygalo

Research output: Contribution to journalArticlepeer-review

Abstract

Adverse factors of early development can produce long-lasting alterations of the brain neurochemical systems, the physiological functions and behavior. Tyrosine hydroxylase (TH), the key enzyme of catecholamine biosynthesis, determines the activity of the neurochemical system and is induced by stress hormones, glucocorticoids, in vitro and in vivo. Analysis of our own data and the data in the literature concerning the effect of stress hormones, glucocorticoids, in the critical periods of perinatal development on the TH gene expression, the level of the protein and the enzyme activity, as well as consideration of the possible mechanisms of these effects, was the purpose of the review. Administration of dexamethasone or hydrocortisone increases the level of TH mRNA in the brainstem of 20-day-old fetuses and 3-day-old rats in 6 hours; it is accompanied by an increase in the enzyme activity and immunohistochemical detection of the TH protein in the brainstem. A change in the TH gene expression in the critical period of early development leads to an increase in the level of TH mRNA in the brainstem of 25- and 70-day-old rats and the enzyme activity in the brainstem and cerebral cortex of adult animals. The period of TH sensitivity to the glucocorticoid level is agedependent. Administration of hormones on the 8th day of the life is not accompanied by changes in the TH mRNA level and the enzyme activity. The promoter of the TH gene does not have a classical functionally active hormone-dependent element. The mechanism of hormonal induction of the TH expression may be based on the noncanonical pathway of the glucocorticoids as a result of the known protein–protein interaction of the glucocorticoid receptor with other transcription factors, such as proteins of the AP-1 complex. This mechanism in the regulation of the TH expression by dexamethasone was found in the pheochromocytoma cell line. The existence of such mechanism in vivo needs to be explored in futher studies.

Original languageEnglish
Pages (from-to)226-234
Number of pages9
JournalRussian Journal of Genetics: Applied Research
Volume7
Issue number3
DOIs
Publication statusPublished - 1 May 2017

Keywords

  • brain
  • gene expression
  • glucocorticoids
  • ontogenetic programming
  • tyrosine hydroxylase

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