title: Reactivation of a hematopoietic endocrine program of pregnancy contributes to recovery from thrombocytopenia.
abstract: Regulation of blood platelet levels involves an array of cytokines, including the placental hormone PRL-like protein E (PLP-E). The PLP-E receptor is present on megakaryocytes in pregnant mice, nonpregnant female mice, and male mice. Other known megakaryocytic cytokines do not share the PLP-E receptor, and thus the presence of this receptor in nonpregnant animals suggests that PLP-E may be expressed in tissues other than the placenta. Consistent with this prediction, PLP-E is produced in thrombocytopenic mouse bone marrow, primarily in granulocytes, but not in normal mouse bone marrow. Serum from thrombocytopenic mice, purified thrombopoietin or IL-6, or pregnancy can induce bone marrow cell expression of PLP-E. The induction of PLP-E gene expression in response to thrombocytopenia is physiologically significant, as injection of PLP-E into thrombocytopenic mice restores normal platelet levels with no effect on granulocytes, erythrocytes, and total white blood cell counts. We conclude that inducible expression of PLP-E in bone marrow is part of the mechanism of recovery from thrombocytopenia. These results also suggest a more general concept: that the endocrine program of pregnancy, which in mammals has evolved to support the intrauterine growth and development of the fetus, can also be harnessed to respond to pathophysiology.
authors.affiliation: Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: Sumit
authors.initials: S
authors.lastname: Bhattacharyya
authors.forename: Jiandie
authors.initials: J
authors.lastname: Lin
authors.forename: Daniel I H
authors.initials: DI
authors.lastname: Linzer
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D008533:Megakaryocytes / Q000378:metabolism; D051379:Mice; D009439:Neuraminidase / Q000378:metabolism; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000378:metabolism* / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000187:drug effects; D013921:Thrombocytopenia / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
chemical_list: D016207:Cytokines; D011257:Pregnancy Proteins; C423011:Prlpe protein, mouse; D012333:RNA, Messenger; D009439:Neuraminidase