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Two Placental Hormones Are Agonists in Stimulating Megakaryocyte Growth and Differentiation

Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208

Address all correspondence and requests for reprints to: Daniel I. H. Linzer, Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, 2153 North Sheridan Road, Evanston, Illinois 60208. E-mail: dlinzer{at}northwestern.edu.

Previously, we demonstrated that a placental hormone, PRL-like protein E, stimulates megakaryocyte growth and differentiation. We now find that PRL-like protein E and a second placental hormone, PRL-like protein F (PLP-F), bind the same receptor. PLP-F, which is produced later in pregnancy, might therefore act as either an agonist or antagonist of PRL-like protein E. To resolve this question, we produced recombinant PLP-F in mammalian cell cultures, purified the secreted glycoprotein hormone, and determined its activity in primary mouse bone marrow cultures. PLP-F induces megakaryocyte differentiation and megakaryocyte progenitor growth in a dose-dependent manner, with significant activity detected at a concentration as low as 50 ng/ml. PLP-F in maternal serum reaches at least 1 µg/ml on gestational d 14.5, and thus the biological activity of PLP-F is detected at physiological concentrations. These results show that PRL-like proteins E and F have the same stimulatory effects on megakaryocyte growth and differentiation, and therefore represent gestation stage-specific agonists.

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