Excessive and Dysregulated Secretion of Prolactin in Rheumatoid Arthritis: Immunopathogenetic and Therapeutic Implications

Abstract

Prolactin (PL) is essential for the normal function of the immune system. It is required for the induction of a number of autoimmune conditions in experimental animals. The role of prolactin in the immunopathogenesis of autoimmune human disease has not been established. RA is characterized by a variety of immune and inflammatory processes which determine disease activity. It has a pronounced diurnal periodicity with a peak at 03.15 hours. Since PL has a diurnal rhythm of secretion in man with a peak at about 02.00 hours, it may contribute to the nocturnal worsening of RA. We show that patients with RA secrete an excess of prolactin as evidenced by an upregulated diurnal periodicity and an abnormal increase in plasma prolactin concentration following surgery. By contrast, patients with chronic osteomyelitis, who had chronic inflammation of similar severity to patients with RA, had a normal prolactin diurnal rhythm and response to surgery. Hence, the abnormal changes in prolactin physiology seen in RA appear to be a feature of the disease per se rather than related to chronic inflammation. The elevated levels of prolactin may contribute to disease activity by augmenting immune processes and may be an additional genetic factor, independent of HLA-DR4, in the immunopathogenesis of RA. Furthermore, the effective inhibition of prolactin secretion and/or action may have potential as therapy for RA.

Thyroid autoimmunity in patients with hyperprolactinemia: an observational study

“…The median PRL in patients was 93 ng/mL (range: 37-470). The median duration of HPRL was 3 years (range: [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. HPRL was caused by prolactinoma in 93 (93%), antipsychotic drugs in 4 (4%), and stalk compression by nonfunctional pituitary adenoma in 3 (3%) patients.…”

“…Besides these diseases linked to abnormal levels of circulating PRL, a role in the pathogenesis of autoimmune diseases has been suggested. Hyperprolactinemia has been often observed in some nonorgan-specific autoimmune diseases, such as systemic lupus erithematosus, rheumatoid artritis, systemic sclerosis, and Sjogren syndrome; moreover, it has been also described in some organ-specific autoimmune diseases, such as type 1 diabetes mellitus, Graves' diseases (GD), Hashimoto's thyroiditis (HT), Addison's disease (AD), lymphocytic hypophysitis (LYH), celiac disease (CD), and multiple sclerosis (MS) (10)(11)(12)(13)(14)(15)(16)(17)(18)(19). But there is still considerable controversy concerning the true immunomodulatory role of PRL, and the subject deserves further investigation.…”

Prolactin Modulates TRPV1 in Female Rat Trigeminal Sensory Neurons

“…A number of painful conditions, known to be more prevalent in women, have been associated with high circulating PRL levels, such as cluster headaches (Waldenlind and Gustafsson, 1987;Talkad et al, 2004), migraines (Silberstein and Merriam, 1993), systemic lupus erythematosous (Walker, 2001;Mendez et al, 2004;Soto et al, 2004), rheumatic arthritis (Chikanza et al, 1993;D'Ambrosia, 2005), and breast pain (mastodynia) (Theunissen et al, 2005). Bromocriptine, a dopamine agonist and inhibitory of pituitary PRL release, has been clinically used to treat these conditions (Kullander and Svanberg, 1979;Walker, 2001;Talkad et al, 2004).…”

A 60 kDa prolactin variant secreted by cervical cancer cells modulates apoptosis and cytokine production

“…Increased PRL levels have been shown in autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis and Sjögren-sindrome (12)(13)(14). Proinflammatory cytokines have the ability to induce pituitary PRL secretion (15), which in turn may contribute to circulating pool of the hormone.…”