Cytokine-like effects of prolactin in human mononuclear and polymorphonuclear leukocytes

Some biochemical events following the binding of prolactin (PRL) to its rec eptor in normal human leukocytes were investigated. PRL enhanced JAK2 phosp horylation in peripheral blood mononuclear cells (PBMC) but not in granuloc ytes. PRL also induced phosphorylation of Stat-5 in PBMC and Stat-1 in gran ulocytes. Subsequent binding of Stat-5- and of Stat-l-like molecules to a G AS responsive element from the P-casein promoter was detected by EMSA. p38 MAPK (but not p42/p44 MAPK) was activated by PRL in both leukocyte populati ons. PRL induced NOS and CIS mRNA expression in granulocytes. Increased exp ression of IRF-1 and SOCS-2 was observed in granulocytes and of SOCS-3 and NOS in PBMC. Similar effects were obtained with ovine and human PRL. Antise rum to PRL reduced NOS and IRF-1 expression induced by PRL in granulocytes and reduced iNOS expression in PBMC. Also, pretreatment of granulocytes wit h a p38 MAPK inhibitor (SB 203580) prevented in part PRL-induced NOS and IR F-1 expression. In PBMC, the p38 inhibitor decreased PRL-induced NOS gene e xpression. These results indicate that PRL-induced gene regulation in leuko cytes requires the activation of at least two different pathways: the Stat and the MAP kinase pathways. Moreover, although PRL activates Stat in both leukocyte types, signal transduction is different in granulocytes and in PB MC. Most importantly, PRL modulates the expression of genes crucial to leuk ocyte function. The present findings reinforce the concept that PRL has "cy tokine- like" activity in human leukocytes. (C) 2001 Elsevier Science B.V. All rights reserved.