Estradiol stimulates gene expression of norepinephrine biosynthetic enzymes in rat locus coeruleus

Lidia Serova, Mark Rivkin, Akira Nakashima, Esther L. Sabban

研究成果: Article査読

103 被引用数 (Scopus)


Gender-specific differences in susceptibility to a number of disorders related to catecholaminergic systems, including depression and hypertension, have been postulated to be mediated, at least in part, by estrogens. In this study, we examined if estrogens may regulate gene expression of norepinephrine biosynthetic enzymes. Administration of five injections of 15 or 40 μg/kg estradiol benzoate to ovariectomized (OVX) female rats elicited a dose-dependent elevation in mRNA levels of tyrosine hydroxylase (TH) in locus coeruleus, to as great as 3-fold over control. Dopamine β-hydroxylase (DBH) mRNA levels were also similarly increased. To examine the mechanism, PC12 cells were cotransfected with luciferase reporter constructs under control of DBH or TH promoters [pDBH/Luc(-2,236/+21) or pTH/Luc(-272/+27 or -773/+27)] with an expression vector for estradiol receptor α. The cells were treated with 17β-estradiol (E2) for 12-36 h. E2 triggered a several fold increase in luciferase activity under control of the DBH promoter in a dose-dependent fashion. Omission of estrogen receptor α or addition of the estrogen receptor antagonist ICI 182,780 prevented the DBH promoter-driven increase in luciferase. When E2 was given with 0.2 mMCPT-cAMP, reporter activity with pDBH/Luc(-2,236/+21) was increased greater than with either treatment alone. In contrast, addition of E2 to cells transfected with pTH/Luc(-272/+27) elicited no change in basal luciferase activity nor in the response to 0.2 mM CPT-cAMP. These findings are the first to reveal that estrogen can stimulate DBH gene expression. Differing mechanisms may underlie the regulation of TH and DBH gene expression by estrogens.

出版ステータスPublished - 2002

All Science Journal Classification (ASJC) codes

  • 内分泌学、糖尿病および代謝内科学
  • 内分泌学
  • 内分泌系および自律システム
  • 細胞および分子神経科学


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