The expression of the proteinase inhibitors of the alpha-macroglobulin family and of their clearance receptor was analyzed in the mouse during pregnancy, embryonal development, and adolescence. In total we studied seven partners of a complicated network of interactions in proteolysis and lipid metabolism:alpha-2-macroglobulin, murinoglobulin, the alpha-2-macroglobulin receptor/lipoprotein receptor related protein, the murine equivalent of the receptor associated protein or the 44 kDa heparin binding protein, the low density lipoprotein receptor, apolipoprotein E, and lipoprotein lipase. The data demonstrate that: i) the regulation of expression of mouse tetrameric alpha-2-macroglobulin results in very constant levels, similar to alpha-2-macroglobulin in humans; ii) single chain murinoglobulin, not alpha-2-macroglobulin, is subject to regulation of expression during pregnancy, around birth, and in adolescence; iii) an important role seems implicated for the alpha-2-macroglobulin receptor in placental lipid metabolism, probably making it the most important lipoprotein receptor to supply the fetus; iv) the massive increase in apolipoprotein E synthesis in uterus and placenta accentuate the changed lipid metabolism during pregnancy to an apolipoprotein E-based uptake by the alpha-2-macroglobulin receptor/lipoprotein receptor related protein; v) the increased expression of lipoprotein lipase underlines its role in the generation of free fatty acids in uterus and placenta as another mechanism of supply, next to receptor mediated endocytosis of lipoproteins.