Eutopic and ectopic macromolecular human placental lactogen

Macromolecular forms of human placental lactogen have received little attention because it has been thought that such forms either compose only a small fraction of total immunoactive placental lactogen or are merely laboratory artifacts. We examined serum and placental tissue from women with normal pregnancy (first and third trimesters), serum and tissue from women with eutopic tumors (mole and choriocarcinoma), and serum from men with ectopic placental lactogen production. Samples were chromatographed on dextran gel (Sephadex G-100), and placental lactogen was measured in the fractions by radioimmunoassay. In all specimens examined, immunoactive placental lactogen was found at the void volume of the column (molecular weight greater than 150,000 daltons). This macromolecular placental lactogen comprised less than 4% of total placental lactogen in the third trimester, in mole, and in 16 of 18 first-trimester samples but was significantly higher, up to 19%, in the malignant cases. In two first-trimester placental extracts (but not in their matched sera) macromolecular placental lactogen was the dominant (greater than 45% of the total placental lactogen) immunoactive species. Authentic monomeric placental lactogen was not converted to macromolecular placental lactogen by repeated freezing and thawing. Third-trimester placental macromolecular placental lactogen was unstable; only 13% remained at the void on rechromatography. First-trimester placental macromolecular placental lactogen, on the other hand, was stable to rechromatography. The behavior of immunochemical dilutions of macromolecular placental lactogen from first-trimester placenta was similar to that of monomeric placental lactogen in the same sample. Macromolecular placental lactogen is probably not artifact, and it can comprise a large fraction of the total immunoactive placental lactogen in certain conditions.