Effects of prolactin on signal transduction and gene expression: possible relevance for systemic lupus erythematosus

Abstract

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.

Cerebrospinal fluid and serum prolactin in systemic lupus erythematosus with and without central nervous system involvement

“…Serum PRL levels were significantly increased in SLE patients compared to healthy controls, especially in active patients, and were positively correlated with SLEDAI, indicating a possible association with SLE disease activity. The above results confirm most of previous research on correlation between serum PRL and SLE disease activity 18–21 …”

Spotlight on the role of hormonal factors in the emergence of autoreactive B-lymphocytes

“…This pathway involves interferon regulating factor-1 (IRF-1) [57], inducible nitric oxide synthase, and suppressors of cytokine signaling (SOCS)-2, -3, and -7 [58]. Prolactin can also activate other signaling pathways, such as the Src and Tec family of tyrosine kinases, SHP-2 phosphatase, ZAP-7, and MAPK and Fyn [54].…”

Stress-Induced versus Preovulatory and Pregnancy Hormonal Levels in Modulating Cytokine Production following Whole Blood Stimulation

“…It has been found that prolactin increases the constitutive expression of SOCS-3 in PBMC, and CIS and SOCS-2 in granulocytes [38] . SOCS-2, however, was found to restore prolactin signaling by interfering with the inhibitory activity of SOCS-1 [37] . Since prolactin receptors are expressed on monocytes as well as other leukocytes, prolactin with LPS might enhance the production of IL-10 from monocytes not only through the JAK-STAT pathway but also from MAPK and/or NF-B, in which expression of SOC-3 does not inhibit the latter two pathways [39] .…”

“…However, in LPS stimulation, prolactin increased IL-10 concentrations which remained elevated even at high concentrations of prolactin. Recently, prolactin was also found to regulate another family of proteins called the suppressors of cytokine signaling (SCOS) [37] . These SOCS proteins (SOCS 1-7 and cytokine-inducible SH2-domain-containing protein CIS) behave like a negative regulator of cytokine signal transduction pathways mainly by inhibiting the JAK-STAT kinase pathway.…”