The induction by estrogen of rat alpha 2u-globulin gene expression in mouse L-cells

Abstract

Expression of the rat 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 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 2u -globulin transcript were induced in stable transfectants of this line carrying a cloned 2u -globulin gene, following exposure to 17 -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 2u -globulin genes. Administration of both dexamethasone and estrogen produced a synergistic effect in this system. The induction of 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.