Ks. Wang et al., THE INDUCTION BY ESTROGEN OF RAT ALPHA(2U)-GLOBULIN GENE-EXPRESSION IN MOUSE L-CELLS, Journal of molecular endocrinology, 20(1), 1998, pp. 141-150
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.