Two placental hormones are agonists in stimulating megakaryocyte growth and differentiation.
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 micro g/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.
Zhou
Beiyan
B
Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208, USA.
Lum
Hillary E
HE
Lin
Jiandie
J
Linzer
Daniel I H
DI
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D016466:CHO Cells; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D016207:Cytokines / Q000494:pharmacology*; D005260:Female; D005333:Fetus; D005865:Gestational Age; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects; D051379:Mice; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000494:pharmacology; D013154:Spleen / Q000166:cytology
D016207:Cytokines; D011257:Pregnancy Proteins; C423011:Prlpe protein, mouse; C502151:Prlpf protein, mouse; D011994:Recombinant Proteins