CELL-SPECIFIC EXPRESSION OF ACTIVIN AND ITS 2 BINDING-PROTEINS IN THERAT DECIDUA - ROLE OF ALPHA(2)-MACROGLOBULIN AND FOLLISTATIN

Rat decidual tissue is formed by two distinct decidual cell population s located either antimesometrially or mesometrially in the uterus. The y differ in morphology, the genes they express, the proteins they secr ete, and the role they play during pregnancy. Recently, we have shown that rat decidua expresses follistatin and alpha(2)-macroglobulin (alp ha(2)-MG), two binding proteins to activin. In the present study, we d etermined whether the decidua of pregnant and pseudopregnant rats also expresses activin, whether activin messenger RNA (mRNA) is confined t o a particular cell population, and whether it is regulated by its bin ding proteins. Decidual and placental tissues were collected at differ ent stages of pseudopregnancy or pregnancy. mRNA expression was examin ed by in situ hybridization, reverse transcription-polymerase chain re action, and Northern analysis. Developmental studies revealed that act ivin A became highly expressed in the antimesometrial decidua only fro m day 11 at a time when this tissue was undergoing extensive degenerat ion. Very little activin A mRNA could be detected in the mesometrial d ecidua. However, late in pregnancy, significant expression of activin A mRNA was detected in the mesometrial decidua undergoing extensive ce ll death at this stage. Developmental study revealed that activin A mR NA became expressed in the antimesometrial decidua only when follistat in mRNA disappeared from this tissue. Furthermore, mesometrial decidua expressing the most alpha(2)-MG mRNA had reduced levels of activin A mRNA. These data suggest that follistatin and alpha(2)-MG may, by bind ing to activin, prevent activin A from stimulating the expression of i ts own gene. To examine this possibility we first established that the rat decidua expresses activin receptor II at a constant level between days 11-15. Then we examined whether follistatin and alpha(2)-MG down -regulate activin expression in a simian virus 40-transformed decidual cell line (GG-AD). These cells express activin A mRNA in abundance, v ery little follistatin, and no alpha(2)-MG. Follistatin and alpha(2)-M G caused a dose-related decrease in activin A mRNA levels in these cel ls. The same inhibitory effect was observed with activin A-blocking an tibody. In summary, the results of this investigation demonstrate that rat decidual tissue expresses mRNAs for activin A and its two binding proteins; follistatin and alpha(2)-MG. The expression of each mRNA is cell specific and developmentally regulated. The finding that both ac tivin-binding proteins and antibody inhibit the expression of activin A in cultured decidual cells suggests that activin regulates its own g ene expression in the decidua. The sequential expression of follistati n first and then activin A in the antimesometrial cells together with the low expression of activin A mRNA in mesometrial cells that express high level alpha(2)-MG mRNA strongly suggest that these two decidua-d erived activin-binding proteins direct the expression pattern and the level of activin A mRNA in the two decidual cell populations during de velopment. High expression of activin A in the decidual cell populatio n undergoing apoptosis suggests a physiological role in the decidual t issue regression and reorganization necessary for fetal development.