Prolactin and its role in stress-induced psoriasis: Milking the data
By Warren R. Heymann, MD
Jan. 18, 2018
Patients will readily acknowledge that stress worsens their psoriasis. When asked how this happens, I respond by mentioning the “mind-body connection” using the term “psychoneuroimmunology;” patients nod in agreement, feigning understanding; appropriately so, because frankly, I don’t understand it either.
The latest data suggests that the bon mot should be “psychoneuroendocrine-immunology” because of the increasing evidence that hormones (corticosteroids, epinephrine, thyroid hormone, insulin, and leptin) may influence psoriasis. The potential role of prolactin in stress-aggravated psoriasis has been the focus of recent attention. (1)
The initial notion that prolactin could worsen psoriasis was considered more than 30 years ago, with the observation that bromocriptine (a dopaminergic agonist that inhibits prolactin secretion) improved or remitted 80% of 60 patients with all variants of psoriasis. (2) Sánchez Regaña et al reported three women with plaque-type psoriasis vulgaris that worsened with development of prolactinomas, which subsequently improved with bromocriptine administration. (3)
Prolactin is a neuropeptide hormone produced by the anterior pituitary, known for its lactogenic, mammotrophic and reproductive effects. It is also produced by extrapituitary tissue (neurons, prostate, decidua, mammary epithelium, immunocompetent cells, skin and hair follicles). Prolactin in vitro stimulates the proliferation of human keratinocytes. Additionally, prolactin acts as a proinflammatory cytokine, enhancing IFN-gamma, IL-12p40 and IL-1-beta production in murine peritoneal macrophages; additionally, IFN-gamma and TNF-alpha production are noted in T cells and peripheral blood mononuclear cells. Hau et al have demonstrated that intraperitoneal prolactin in mice enhances the expression of Th17 and Th1 cytokines/chemokines, thereby augmenting inflammation in imiquimod-induced psoriasiform skin. The authors concluded that prolactin may exacerbate psoriasis via the enhancement of Th17/Th1 responses. (4)
Increased levels of prolactin have been associated with psychoemotional stress. (5) Multiple manuscripts have associated elevated serum prolactin levels with other autoimmune diseases including systemic lupus erythematosus, systemic sclerosis, Reiter syndrome, rheumatoid arthritis, diabetes mellitus, Addison disease, and autoimmune thyroiditis. (6)
There have numerous studies in the literature measuring prolactin levels in patients with psoriasis, yielding conflicting data. Lee et al performed a meta-analysis comparing serum/plasma prolactin (PRL) levels in patients with psoriasis with those of healthy controls (HCs,) and correlating circulating PRL levels to psoriasis severity based on Psoriasis Area and Severity Index (PASI). In total, 12 studies assessing 446 patients with psoriasis and 401 HCs were included. PRL levels were significantly higher in the psoriasis group than in the HC group (P < 0.01). Stratification by age and sex also revealed a significantly higher PRL level in the psoriasis group (P < 0.01). Subgroup analysis by sample size showed a significantly higher PRL level with larger sample sizes (n ≥ 80) (P = 0.02), but not with smaller sample sizes (n < 80) in the psoriasis group. Meta-analysis of the correlation coefficients showed a positive, although not statistically significant, correlation between circulating PRL levels and PASI (P = 0.08). The authors concluded that circulating PRL levels are higher in patients with psoriasis, and PRL levels may correlate with psoriasis severity. (7)
More research is warranted in unraveling the mysterious relationship between nerves, hormones, inflammatory cells, and skin. Prolactin may be an integral piece of the puzzle. Solving this riddle will inevitably lead to novel therapeutic interventions for psoriasis and other autoimmune disorders aggravated by stress. In the meanwhile, turning off cable news and listening to classical music might help!
(I anticipate that prolactin levels will be peaking in the Delaware Valley Sunday night — Go E-A-G-L-E-S!)
1. Roman II, et al. The role of hormones in the pathogenesis of psoriasis vulgaris. Clujul Med 2016; 89: 11-18.
2. Weber G, et al. Treatment of psoriasis with bromocriptin. Arch Dermatol Res 1981; 271: 437-9.
3. Sánchez Regaña M, Umbert Millet P. Psoriasis in association with prolactinoma: three cases. Br J Dermatol 2000; 143: 864-7.
4. Hau CS, et al. Prolactin induces the production of Th17 and Th1 cytokines/chemokines in murine imiquimod-induced psoriasiform skin. J Eur Acad Dermatol Venereol 2014; 28: 1370-9.
5. Langan EA, Griffiths CEM. Exploring the role of prolactin in psoriasis. Arch Dermatol Res 2012; 304: 115-8.
6. Botezatu D, Interplay between prolactin and pathogenesis of psoriasis vulgaris. Maedica (Buchar) 2016; 11: 232-40.
7. Lee YH, Song GG. Association between circulating prolactin levels and psoriasis and its correlation with disease severity. Clin Exp Dermatol 2018; 43: 27-35.
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