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 t he adult male liver by a number of hormones, including growth hormone, thyroid hormone and several steroids. Upon injection into ovariectomi zed 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 expres sed 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-estra diol. Since this induction was inhibited by cycloheximide, the respons e to estrogen, as to other steroids, appears to be secondary. Using ge nes with variously deleted 5'-upstream regions, sequences responsible for this induction were located between -730 bp and -223 bp relative t o the start of transcription. Examination of the DNA in this region re vealed 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 synergist ic effect in this system. The induction of alpha(2u)-globulin RNA by e strogen in L-cells may re-capitulate the initial response to estrogen in vivo, and therefore represents a good model system to seek the iden tity of the other factors required to effect full induction.