ESTROGENIC EFFECT ON THE EXPRESSION OF ESTROGEN-RECEPTOR, COUP-TF, AND LACTOFERRIN MESSENGER-RNA IN DEVELOPING MOUSE-TISSUES

We have previously demonstrated that lactoferrin (LF) is a major estro gen-inducible protein in the mouse uterus. The increase of LF mRNA aft er estrogen treatment (>300 fold) is the result of a complex interplay among transcription factors acting on the estrogen response element ( ERE) of the LF gene. Two transcription factors - the estrogen receptor (ER) and the chicken ovalbumin upstream promoter transcription factor (COUP-TF) - play opposing roles in the estrogen responsiveness of the LF gene promoter-reporter constructs in transiently transfected human endometrial carcinoma cells, The ratio of ER/COUP-TF in the transfect ed cells appears to be critical for estrogen-stimulated LF gene promot er activity (Liu et al, 1993), In the current study, ER and COUP-TF mR NA levels are examined and related to LF mRNA expression in various mo use tissues, including the developing uterus with/without estrogen sti mulation. Results show that LF mRNA and protein are expressed in vario us tissues during development, but the potent synthetic estrogen, diet hylstilbestrol (DES), does not increase LF mRNA expression in nonrepro ductive tissues such as liver, spleen, and lung. In contrast, in devel oping neonatal reproductive tract tissues, DES increases LF mRNA and p rotein expression as previously reported in immature and mature uterin e tissues. DES, however, did not affect ER and COUP-TF expression in d eveloping uterine tissues. Although the uterus has a high ratio of ER/ COUP-TF as compared to other tissues examined, COUP-TF may not be the only regulator for LF gene expression in this particular tissue since COUP-TF remains constant during development and following DES treatmen t. These data point to the complexity of differential expression of LF gene in estrogen responsive and nonresponsive tissues during developm ent. (C) 1996 Wiley-Liss, Inc.