The proposed research is an investigation of two mouse hormones, placental lactogen I and placental lactogen II. The synthesis of these hormones, which are members of the prolactin/growth hormone family, occurs specifically in the placenta and at discrete stages of gestation. These hormones bind to the prolactin receptor, and are active in assays for prolactin-like mitogenic and lactogenic effects. The long-term objectives of this research are to understand the functions of these hormones in the development of the embryo and in the pregnancy-related changes in the mother; the immediate goal is to generate reagents for studying the placental lactogens. These goals include the expression of cDNAs for each placental lactogen in cultured mouse cells, and the purification of these proteins; and the construction and expression of altered placental lactogen cDNA sequences encoding mutant proteins. The antibodies and mutant proteins will be used to map the essential regions of these hormones for receptor binding and biological activity. Another goal of this research is to establish placental-derived cell lines that synthesize and secrete placental lactogens. The establishment of such cell lines would enable an investigation of the regulation of hormone expression (from the transcription of these genes to the secretion of the synthesized proteins) in a well- defined system. Attempts to generate these cell lines will involve the use of placental-specific gene promoters linked to immortalizing genes. The known effects of hematopoietic growth factors on placental trophoblast cell growth will also be examined to determine if cells responding to these factors also are producing the hormones of interest. The placental lactogens appear to be released rapidly after synthesis, unlike prolactin and growth hormone. The possibility that these placental proteins have different signals for storage and secretion than the related pituitary hormones will be investigated by expression of placental lactogen I and II in a cell line that displays regulated secretion of various protein hormones. Finally, the genes encoding placental lactogen I and II will be characterized, with the goal of defining elements governing placental-specific expression.

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Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
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Biochemical Endocrinology Study Section (BCE)
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Northwestern University at Chicago
Schools of Arts and Sciences
United States
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Bhattacharyya, Sumit; Lin, Jiandie; Linzer, Daniel I H (2002) Reactivation of a hematopoietic endocrine program of pregnancy contributes to recovery from thrombocytopenia. Mol Endocrinol 16:1386-93
Zhou, Beiyan; Lum, Hillary E; Lin, Jiandie et al. (2002) Two placental hormones are agonists in stimulating megakaryocyte growth and differentiation. Endocrinology 143:4281-6
Toft, D J; Rosenberg, S B; Bergers, G et al. (2001) Reactivation of proliferin gene expression is associated with increased angiogenesis in a cell culture model of fibrosarcoma tumor progression. Proc Natl Acad Sci U S A 98:13055-9
Lefebvre, P; Lin, J; Linzer, D I et al. (2001) Murine prolactin-like protein E synergizes with human thrombopoietin to stimulate expansion of human megakaryocytes and their precursors. Exp Hematol 29:51-8
Lin, J; Toft, D J; Bengtson, N W et al. (2000) Placental prolactins and the physiology of pregnancy. Recent Prog Horm Res 55:37-51; discussion 52
Bengtson, N W; Linzer, D I (2000) Inhibition of tumor growth by the antiangiogenic placental hormone, proliferin-related protein. Mol Endocrinol 14:1934-43
Toft, D J; Linzer, D I (2000) Identification of three prolactin-related hormones as markers of invasive trophoblasts in the rat. Biol Reprod 63:519-25
Lin, J; Linzer, D I (1999) A novel megakaryocyte differentiation factor from mouse placenta. Trends Cardiovasc Med 9:167-71
Lin, J; Linzer, D I (1999) Induction of megakaryocyte differentiation by a novel pregnancy-specific hormone. J Biol Chem 274:21485-9
Toft, D J; Linzer, D I (1999) Prolactin (PRL)-like protein J, a novel member of the PRL/growth hormone family, is exclusively expressed in maternal decidua. Endocrinology 140:5095-101

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