EXPRESSION OF ALPHA-2-MACROGLOBULIN RECEPTOR LOW-DENSITY-LIPOPROTEIN RECEPTOR-RELATED PROTEIN AND THE 39-KD RECEPTOR-ASSOCIATED PROTEIN IN HUMAN TROPHOBLASTS

The alpha(2)-macroglobulin receptor/low density lipoprotein receptor-r elated protein (alpha(2)MR/LRP) and its 39-kd receptor-associated prot ein CRAP) were identified by indirect immunofluorescence in human extr avillous and villous trophoblast cells at different stages of pregnanc y. The (alpha(2)MR/LRP was detected in invading trophoblast cells and in some instances these invading cells did not express RAP. In chorion ic villi of first and second trimester placenta, alpha(2)MR/LRP and RA P were found in cytotrophoblast and syncytiotrophoblast. With advancin g Pregnancy alpha(2)MR/LRP became primarily localized to the apical su rface of the syncytiotrophoblast, while RAP was present in the cytopla sm Villous cytotrophoblast cells lost both proteins by the third trime ster. Isolated cytotrophoblast cells that undergo spontaneous differen tiation into syncytiotrophoblast in culture increased expression of bo th alpha(2)MR/LRP and RAP. With syncytium formation, alpha(2)MR/LRP be came localized to the plasma membrane in culture structures. Changes i n the mRNAs for alpha(2)MR/LRP and RAP paralleled the changes in relat ive abundance of the proteins assessed by immunofluorescence. cAMP tre atment suppressed both alpha(2)MR/LRP and RAP in the cultured trophobl asts, but alpha(2)MR/LRP was reduced to a greater extent than RAP. We conclude that alpha(2)MR/LRP and RAP are developmentally regulated in human tropho-blast cells, that the temporal and sapatial patterns of e xpression of these proteins can be dissociated, and that cAMP modulate s both alpha(2)MR/LRP and RAP in human trophoblast. The patterns of al pha(2)MR/LRP and RAP expression ill trophoblast cells are consistent w ith roles for the receptor in trophoblast invasion and transport of mo lecules across the syncytiotrophoblast.