Estrogen Receptor α Regulates Expression of the Orphan Receptor Small Heterodimer Partner

Autor: Mark J. Evans, Douglas C. Harnish, KehDih Lai
Rok vydání: 2003
Předmět:
Male
Time Factors
Receptors
Cytoplasmic and Nuclear
Estrogen receptor
Biochemistry
Rats
Sprague-Dawley
Mice
Cholesterol 7-alpha-Hydroxylase
Promoter Regions
Genetic
Mice
Knockout
Orphan receptor
Estradiol
Reverse Transcriptase Polymerase Chain Reaction
hemic and immune systems
Cell biology
DNA-Binding Proteins
Liver
Receptors
Estrogen
embryonic structures
Small heterodimer partner
biological phenomena
cell phenomena
and immunity
Dimerization
Plasmids
Protein Binding
animal structures
Molecular Sequence Data
chemical and pharmacologic phenomena
Biology
Transfection
Cholesterol 7 alpha-hydroxylase
Cell Line
Phenols
Animals
Humans
Steroid 12-alpha-Hydroxylase
RNA
Messenger
Molecular Biology
Transcription factor
Hormone response element
Binding Sites
Base Sequence
Dose-Response Relationship
Drug
Estrogen Receptor alpha
Cell Biology
Protein Structure
Tertiary
Rats
Gene Expression Regulation
Nuclear receptor
Mutation
Cancer research
Pyrazoles
RNA
Farnesoid X receptor
Gene Deletion
Transcription Factors
Zdroj: Journal of Biological Chemistry. 278:36418-36429
ISSN: 0021-9258
DOI: 10.1074/jbc.m303913200
Popis: Hormonal status can influence diverse metabolic pathways. Small heterodimer partner (SHP) is an orphan nuclear receptor that can modulate the activity of several transcription factors. Estrogens are here shown to directly induce expression of the SHP in the mouse and rat liver and in human HepG2 cells. SHP is rapidly induced within 2 h following treatment of mice with ethynylestradiol (EE) or the estrogen receptor alpha (ERalpha)-selective compound propyl pyrazole triol (PPT). SHP induction by these estrogens is completely absent in ERalphaKO mice. Mutation of the human SHP promoter defined HNF-3, HNF-4, GATA, and AP-1 sites as important for basal activity, whereas EE induction required two distinct elements located between -309 and -267. One of these elements contains an estrogen response element half-site that bound purified ERalpha, and ERalpha with a mutated DNA binding domain was unable to stimulate SHP promoter activity. This ERalpha binding site overlaps the known farnesoid X receptor (FXR) binding site in the SHP promoter, and the combination of EE plus FXR agonists did not produce an additive induction of SHP expression in mice. Surprisingly, induction of SHP by EE did not inhibit expression of the known SHP target genes cholesterol 7alpha-hydroxylase (CYP7A1) or sterol 12alpha-hydroxylase (CYP8B1). However, the direct regulation of SHP expression may provide a basis for some of the numerous biological effects of estrogens.
Databáze: OpenAIRE
Externí odkaz: