Effect of Estrogens with ERα or ERβ on Transcriptional Regulation of Catecholamine Biosynthetic Enzymes

Abstract

Estrogen is proposed to be responsible for some of the gender specific differences in susceptibility to several disorders relating to catecholaminergic systems. Previously, administration of estrogen to rats in vivo was found to alter mRNA levels of catecholamine (CA) biosynthetic enzymes, TH and DBH, as well as GTPCH, rate limiting for tetrahydrobiopterin (cofactor for TH, TPH and NOS). However, there were differences depending on the dose and mode of administration and the tissue examined. Prolonged estrogen injections also attenuated some of the stress triggered changes in gene expression of CA biosynthetic enzymes. Since the different responses might reflect changes in ER subtype expressed, we transfected PC12 cells with either ERα or ERβ and reporter vectors for TH, DBH or GTPCH. Treatment with 2.5-20 nM 17 β-estradiol (E2) elevated TH, DBH or GTPCH promoter driven luciferase activities with ERα. However, with ERβ, E2 decreased TH, and increased DBH and GTPCH promoter activities. The promoter elements involved are being identified. We examined the combined response to E2 and elevated cAMP. Their effects were additive on DBH promoter activity. However E2 attenuated the elevation of TH and GTPCH transcription in response to cAMP analogs with either ER. Thus, the ER subtype expressed can influence transcriptional regulation of CA systems.