Effects of prolactin on signal transduction and gene expression: possible relevance for systemic lupus erythematosus.
Receptors for prolactin (PRL-R) are expressed in normal leukocytes from rat and man. PRL signals through PRL-R associated Janus tyrosine kinase (Jak)-2 and signal transducers and activators of transcription (Stat). In addition, in human leukocytes PRL also activates the p38 MAP kinase pathway. PRL, at physiological concentrations, stimulates the expression of the interferon regulatory factor (IRF)-1 gene in rat spleen and bone marrow cells. In man, genes induced by PRL include several members of the 'suppressors of cytokine signaling' (SOCS) family and inducible nitric oxide synthase (iNOS; in mononuclear cells and in granulocytes) and IRF-1 (in granulocytes). Thus, in normal leukocytes, PRL induces the expression of several genes relevant to innate and acquired immune responses. Sex hormones, such as estrogen and PRL, have been implicated in the pathogenesis of murine and human SLE. Also defective signaling in leukocytes is a feature of the disease. What the origin is of aberrant signaling processes in SLE lymphocytes and how they relate to tolerance breakdown and immunopathology is still unknown. It is not unlikely that PRL is a player at some level. The exact contribution of PRL to immune responses in normal subjects and in SLE patients is not known. Further work should also indicate whether PRL might contribute to the onset or progression of the disease and assess the possible benefits of manipulating PRL concentrations in patients.
Hooghe
R
R
Pharmacology Department, Medical School, Free University of Brussels (VUB), Belgium.
Dogusan
Z
Z
Martens
N
N
Velkeniers
B
B
Hooghe-Peters
E L
EL
D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D007107:Immune System / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D011981:Receptors, Prolactin / Q000378:metabolism; D015398:Signal Transduction
D011981:Receptors, Prolactin; D011388:Prolactin