Prolactin in Autoimmune Diseases
Prolactin in Autoimmune Diseases
European Endocrine Disease 2006 Issue 2
Published: October 2008
Published: October 2008
Prolactin (PRL) enhances the progression of the immune process in autoimmune diseases because of its involvement in many immunological activations. PRL is a versatile hormone, now recognised as a cytokine, produced not only by the anterior pituitary gland, but also by extra pituitary sites (neurons, prostate, deciduas mammary epithelium, endothelial cells and skin cells), including immune cells. PRL is important in maintaining immune competences and in playing an important role in immune response by autocrine-paracrine mechanisms. The initial step of PRL action in the immune system is binding to a specific membrane receptor, expressed on the immune and haemopoietic cells. These receptors are included as members of the cytokine receptor superfamily such as receptors for interleukin (IL)2β, IL3, IL4, IL6, IL7.
PRL plays an important bidirectional role in the autoimmune process between the neuroendocrine and the immune system. In fact, inflammatory cytokine released in the autoimmune process are able not only to active the hypothalamus-pituitaryadrenal axis (the corticosteroid inhibits cytokine production), but also to induce release of pituitary and paracrine PRL that may counteract with immunosuppressive hormones, as steroids.
PRL and Autoimmune Diseases
Hyperprolactinaemia (HPRL) has been observed in some non organ-specific autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SS) and Sjogren’s syndrome; moreover, it has been described in some organ-specific autoimmune diseases as type 1 diabetes mellitus, Graves disease, Hashimoto’s thyroiditis (HT), Addison’s disease, lymphocytic hypophysitis (LYH), coeliac disease and multiple sclerosis (MS).
This correlation could depend on a co-ordinated bidirectional communication between neuroendocrine and the immune disease. The relationship between PRL and autoimmune diseases could be also explained by taking into account that the human PRL gene is located on the short-term of the chromosome 6, close to the human leukocyte antigen (HLA) region. It is well known that some antigens of the HLA complex are correlated to higher frequency of many autoimmune diseases. PRL stimulates the release of both T helper 1 and T helper 2 cytokines, involved in the pathogenesis of these diseases.
In particular, PRL increases the production of interferon-gamma (INFγ) by lymphocytes and induces the expression of the IL2 receptors on the surface of lymphocytes. Therefore, PRL activates Tlymphocytes with the Th2 profile that stimulate the autoantibody production as islet cell antibodies (ICA), thyroglobulin antibodies (TgAb), thyroperoxidase antibodies (TPOAb), adrenocortical antibodies (ACA) and transglutaminase antibodies (tTGAb) in all the above-mentioned diseases. Of particular interest is the evidence of HPRL in the active phase of the organ and non-organ autoimmune disease.
