Elsevier

Autoimmunity Reviews

Volume 1, Issue 6, December 2002, Pages 360-364
Autoimmunity Reviews

Prolactin and autoimmunity

https://doi.org/10.1016/S1568-9972(02)00081-2Get rights and content

Abstract

Prolactin (PRL) is a versatile hormone that is produced by the anterior pituitary gland and various extrapituitary sites including immune cells. Furthermore, PRL has widespread influences on proliferation and differentiation of a variety of cells in the immune system and is, in effect, a cytokine. PRL-receptors (PRL-R) are distributed throughout the immune system and are included as members of the cytokine receptor superfamily. PRL-R signal transduction is mediated by a complex array of signaling molecules of which JAK2, Stat1 and Stat5 pathway have been well studied. In PRL-stimulated T cells, the transcription factor gene, interferon regulatory factor-1 provides a mechanism whereby PRL can regulate the immune response. The human PRL gene is situated on the short arm of chromosome 6 close to the major histocompatibility complex. Polymorphisms of the human PRL gene have implications for production of lymphocyte PRL in SLE. Mild and moderate hyperprolactinemia (HPRL) has been demonstrated in 20–30% of SLE patients and is associated with active disease. HPRL may have a role in lupus nephritis and central nervous system involvement of SLE patients. HPRL stimulated the production of autoantibodies. These evidences support the important role of PRL in autoimmunity and autoimmune diseases, mainly SLE.

Introduction

Prolactin (PRL), a versatile hormone with more than 300 separate functions, is produced in the anterior pituitary gland and affects mammary growth and differentiation and its secretion is mediated via the dopaminergic pathway. It is now recognized that PRL is a cytokine and is produced in a number of extrapituitary sites, including neurons, prostate, decidua, mammary epithelium, endothelial cells, skin cells, and immune cells. PRL is important to maintain immune competence and plays an important role in animal and human immune response [1], [2].

Section snippets

PRL and immune system

PRL is know to regulate cellular function including proliferation, differentiation, angiogenesis, and protection against apoptosis and inflammation. The initial step of PRL action is the binding to a specific membrane receptors. PRL-receptors (PRL-R) are distributed throughout the immune system and are included as members of the cytokine receptor superfamily such as receptors for interleukin (IL)-2 beta chain, IL-3, IL-4, IL-6, IL-7, growth hormone (GH), and erytropoietin [3], [4].

PRL, immune system, and systemic lupus erythematosus

Hyperprolactinemia (HPRL) has been confirmed in SLE (20–30%), however, the association between HPRL with active disease is controversial. This discrepant finding maybe explained by different factors such as: statistical power of these studies, heterogeneous groups of patients, variability of the SLE activity indices used, anti-PRL antibodies, etc. [19]. However, new evidence has confirmed a significant correlation between serum PRL levels and activity on SLE [20], [21], [22].

In summary

Accumulated evidence within the past decade and during the first years of this century, has increased our understanding of PRL, PRL-R, transduction signals and genetic polymorphism within cells of the immune system. The initial clinical observations of HPRL associated with active SLE has been confirmed. Further studies to establish the connection between the basic and clinical observations are necessary to understand the role of PRL in the pathogenesis of SLE and other autoimmune diseases.

The

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