Ta. Tibbetts et al., MUTUAL AND INTERCOMPARTMENTAL REGULATION OF ESTROGEN-RECEPTOR AND PROGESTERONE-RECEPTOR EXPRESSION IN THE MOUSE UTERUS, Biology of reproduction, 59(5), 1998, pp. 1143-1152
The epithelial and stromal compartments of the uterus undergo signific
ant estrogen- and progesterone (P-4)-induced changes during the estrou
s cycle. While in the adult mouse, epithelial proliferation and stroma
l inflammation are induced by estrogen, P-4 is antiproliferative in th
e epithelium and both proliferative and anti-inflammatory in the strom
a. In light of these compartmentally varying roles, we have immunohist
ochemically examined estrogen and P-4 regulation of the expression of
their receptors (ER and PR) and their epithelial target gene lactoferr
in (LF) in wild-type and PR null mutant mice. We demonstrate that estr
ogen exerts compartment-specific effects on the expression of ER, resu
lting in decreased levels of stromal and glandular epithelial (GE) ER
and increased luminal epithelial (LE) and myometrial ER. Estrogen also
has dual effects on PR expression, decreasing levels in the LE while
at the same time increasing levels in the stroma and myometrium. Estro
gen and P-4 together mediate their effects in part through the ability
of P-4 to selectively inhibit myometrial ER expression while preservi
ng CE expression. We also demonstrate a general negative feedback by P
-4 on PR expression that is most prominent in the GF. Finally, we demo
nstrate using the estrogen- and P-4-responsive epithelial target gene
LF that the differential regulation of PR in the glandular and luminal
epithelium results in different functional responses of these compart
ments to P-4. Together, our data indicate that the pleiotropic effects
of estrogen and P-4 in the adult mouse uterus are mediated by complex
hormonal interregulation of ER and PR in specific uterine compartment
s.