THE DECIDUAL PROLACTIN RECEPTOR AND ITS REGULATION BY DECIDUA-DERIVEDFACTORS

Decidualization of the endometrial stroma in the rat gives rise to two different cell populations, located either mesometrially or antimesom etrially in the uterus. We have previously shown that the rat decidua is the site of production and action of a PRL-like hormone. In this in vestigation we examined, using reverse transcription-PCR, whether and which type of PRL receptor (PRL-R) messenger RNA (mRNA) is expressed i n the decidua, whether the receptor is confined only to one cell popul ation, and whether the PRL-R expression is regulated by decidua-derive d factors. The results indicate that the uterus of pseudopregnant rats does not express the PRL-R and that decidualization does not trigger a rapid appearance of PRL-R mRNA. It is only 3 days after the inductio n of decidualization that the long form of the PRL-R was first express ed. Thereafter, mRNAs for both the short (PRL-R(S)) and the long (PRL- R(L) form became detectable in both antimesometrial and mesometrial de cidua, although PRL-R(L) mRNA was much more abundant than PRL-R(S). As development proceeded, PRL-R mRNA decreased and disappeared specifica lly from the antimesometrial decidua, whereas the mesometrial decidua continued to express this receptor mRNA. Concomitant with down-regulat ion of the PRL-R in the antimesometrial tissue was a rather abrupt exp ression of activin A. In contrast, the mesometrial tissue that maintai ned high levels of PRL-R mRNA expressed little activin A, but produced an activin-binding protein, alpha(2)-macroglobulin (alpha(2)MG). To d etermine whether activin A and alpha(2)MG regulate PRL-R expression, a ntimesometrial and mesometrial cells were separated by elutriation and maintained in culture in the presence or absence of activin A, alpha( 2)MG, or follistatin. Just after cell separation, both cell population s expressed PRL-R, but not activin A. Within 6 h, activin A mRNA and p rotein became highly expressed in the mesometrial cells, whereas PRL-R , mRNA became undetectable. In contrast, activin A mRNA was at very lo w levels in the antimesometrial cells, and no activin A protein could be detected in the medium for at least 12 h. In these cells PRL-R, mRN A remained elevated. Addition of activin A to antimesometrial cells ca used a marked down-regulation of PRL-R, mRNA expression, whereas addit ion of alpha(2)MG and follistatin to mesometrial cells prevented the d isappearance of PRL-R. In summary, the results of this investigation 1 ) indicate that decidualization of the endometrial stroma induces the appearance of both forms of the PRL-R mRNAs; 2) show differential expr ession of the PRL-R mRNA in the two-cell population forming the decidu a; 3) establish that this differential expression is due to two key de cidual molecules, activin A and alpha(2) macroglobulin; and 4) demonst rate that activin A can cause the decidual cells to lose the PRL-R and that the disappearance of the decidual PRL-R can be prevented by addi tion to the culture of two activin binding proteins, follistatin and a lpha(2)MG.