The induction by estrogen of rat alpha 2u-globulin gene expression in mouse L-cells.
Expression of the rat alpha 2u-globulin gene family is regulated in the adult male liver by a number of hormones, including growth hormone, thyroid hormone and several steroids. Upon injection into ovariectomized females, estrogens first induce alpha 2u-globulin expression and then suppress this gene after several days of hormone administration. To study this phenomenon, we developed a mouse L-cell line that expressed the human estrogen receptor. High levels of rat alpha 2u-globulin transcript were induced in stable transfectants of this line carrying a cloned alpha 2u-globulin gene, following exposure to 17 beta-estradiol. Since this induction was inhibited by cycloheximide, the response to estrogen, as to other steroids, appears to be secondary. Using genes with variously deleted 5'-upstream regions, sequences responsible for this induction were located between -730 bp and -223 bp relative to the start of transcription. Examination of the DNA in this region revealed that an estrogen receptor element was located at -590 bp in an area that is highly conserved in most known alpha 2u-globulin genes. Administration of both dexamethasone and estrogen produced a synergistic effect in this system. The induction of alpha 2u-globulin RNA by estrogen in L-cells may re-capitulate the initial response to estrogen in vivo, and therefore represents a good model system to seek the identity of the other factors required to effect full induction.
Wang
K S
KS
Department of Biological Sciences, University of Alberta, Edmonton, Canada.
Hodgetts
R B
RB
Addison
W R
WR
D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D003907:Dexamethasone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects; D000511:alpha-Macroglobulins / Q000235:genetics*
D012333:RNA, Messenger; D000511:alpha-Macroglobulins; D004958:Estradiol; D003907:Dexamethasone