Skip to main content

Advertisement

SpringerLink
Log in

Prolactin and Autoimmunity

  • Published:
Clinical Reviews in Allergy & Immunology Aims and scope Submit manuscript

Abstract

The relationship between prolactin and the immune system has been demonstrated in the last two decades, opening new windows in the field of the immunoendocrinology. Prolactin has an important role in the innate and adaptive immune response. Increased prolactin levels have been described in autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, Sjögren syndrome, and systemic sclerosis among others. Hyperprolactinemia is associated with active disease and organ involvement in systemic lupus erythematosus. Therefore, prolactin is an integral member of the immunoneuroendocrinology network and seems to have a role in pathogenesis of autoimmune diseases. Few controlled studies of dopamine agonist treatment in humans with autoimmune disease have been conducted only in systemic lupus erythematosus patients, which support the potential efficacy of such agents even during pregnancy and postpartum. Further studies are necessary to elucidate the mechanisms by which prolactin affects autoimmune disease activity, increase the inflammatory mechanism, and determine the role of anti-prolactinemic drugs to regulate the immune/inflammatory process.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Jara LJ, Lavalle C, Fraga A et al (1991) Prolactin, immunoregulation, and autoimmune diseases. Semin Arthritis Rheum 20:273–284

    Article  CAS  PubMed  Google Scholar 

  2. De Bellis A, Bizzarro A, Pivonello R, Lombardi G, Bellastella A (2005) Prolactin and autoimmunity. Pituitary 8:25–30

    Article  CAS  PubMed  Google Scholar 

  3. Berczi I, Quintanar-Stephano A, Kovacs K (2009) Neuroimmune regulation in immunocompetence, acute illness, and healing. Ann N Y Acad Sci 1153:220–239

    Article  CAS  PubMed  Google Scholar 

  4. Wu H, Devi R, Malarkey WB (1996) Expression and localization of prolactin messenger ribonucleic acid in the human immune system. Endocrinology 137:349–353

    Article  CAS  PubMed  Google Scholar 

  5. Vera-Lastra O, Jara LJ, Espinoza LR (2002) Prolactin and autoimmunity. Autoimmun Rev 1:360–364

    Article  CAS  PubMed  Google Scholar 

  6. Adamson AD, Friedrichsen S, Semprini S et al (2008) Human prolactin gene promoter regulation by estrogen: convergence with tumor necrosis factor-alpha signaling. Endocrinology 149:687–694

    Article  CAS  PubMed  Google Scholar 

  7. Ben-Jonathan N, LaPensee CR, LaPensee EW (2008) What can we learn from rodents about prolactin in humans? Endocr Rev 29:1–41

    Article  CAS  PubMed  Google Scholar 

  8. Clapp C, Thebault S, Arnold E, García C, Rivera JC, de la Escalera GM (2008) Vasoinhibins: novel inhibitors of ocular angiogenesis. Am J Physiol Endocrinol Metab 295:E772–E778

    Article  CAS  PubMed  Google Scholar 

  9. Vlahos NP, Bugg EM, Shamblott MJ, Phelps JY, Gearhart JD, Zacur HA (2001) Prolactin receptor gene expression and immunolocalization of the prolactin receptor in human luteinized granulosa cells. Mol Hum Reprod 7:1033–1038

    Article  CAS  PubMed  Google Scholar 

  10. Tomio A, Schust DJ, Kawana K et al (2008) Prolactin can modulate CD4+ T-cell response through receptor-mediated alterations in the expression of T-bet. Immunol Cell Biol 86:616–621

    Article  CAS  PubMed  Google Scholar 

  11. Redelman D, Welniak LA, Taub D, Murphy WJ (2008) Neuroendocrine hormones such as growth hormone and prolactin are integral members of the immunological cytokine network. Cell Immunol 252:111–121

    Article  CAS  PubMed  Google Scholar 

  12. Orbach H, Shoenfeld Y (2007) Hyperprolactinemia and autoimmune diseases. Autoimmun Rev 6:537–542

    Article  CAS  PubMed  Google Scholar 

  13. De Bellis A, Bizarro A, Bellastrella A (2008) Prolactin and autoimmunity. In: Walker S, Jara LJ (eds) Endocrine manifestations of systemic autoimmune diseases. Handbook of systemic autoimmune diseases, vol. 9. Elsevier, Amsterdam, pp 29–43

    Google Scholar 

  14. Walker SE, Jacobson JD (2000) Roles of prolactin and gonadotropin-releasing hormone in rheumatic diseases. Rheum Dis North Am 26:713–736

    Article  CAS  Google Scholar 

  15. Jara LJ, Gomez-Sanchez C, Silveira LH, Martinez-Osuna P, Vasey FB, Espinoza LR (1992) Am J Med Sci 303:222–226

    Article  CAS  PubMed  Google Scholar 

  16. Jara LJ, Vera-Lastra O, Miranda JM, Alcala M, Alvarez-Nemegyei J (2001) Prolactin in human systemic lupus erythematosus. Lupus 10:748–756

    Article  CAS  PubMed  Google Scholar 

  17. Rovenský J, Juránková E, Rauová L et al (1997) Relationship between endocrine, immune, and clinical variables in patients with systemic lupus erythematosus. J Rheumatol 24:2330–2334

    PubMed  Google Scholar 

  18. McMurray RW, Allen SH, Braun AL, Rodriguez F, Walker SE (1994) Longstanding hyperprolactinemia associated with systemic lupus erythematosus: possible hormonal stimulation of an autoimmune disease. J Rheumatol 21:843–850

    CAS  PubMed  Google Scholar 

  19. Reuman PD (2004) First reported pediatric case of systemic lupus erythematosus associated with prolactinoma. Arthritis Rheum 50:3616–3618

    Article  PubMed  Google Scholar 

  20. Li M, Keiser HD, Peeva E (2006) Prolactinoma and systemic lupus erythematosus: do serum prolactin levels matter? Clin Rheumatol 25:602–605

    Article  PubMed  Google Scholar 

  21. Freemark M, Driscoll P, Maaskant R, Petryk A, Kelly PA (1997) Ontogenesis of prolactin receptors in the human fetus in early gestation. Implications for tissue differentiation and development. J Clin Invest 99:1107–1117

    Article  CAS  PubMed  Google Scholar 

  22. Leaños-Miranda A, Chávez-Rueda KA, Blanco-Favela F (2001) Biologic activity and plasma clearance of prolactin–IgG complex in patients with systemic lupus erythematosus. Arthritis Rheum 44:866–875

    Article  PubMed  Google Scholar 

  23. Pacilio M, Migliaresi S, Meli R, Ambrosone L, Bigliardo B, Di Carlo R (2001) Elevated bioactive prolactin levels in systemic lupus erythematosus—association with disease activity. J Rheumatol 28:2216–2221

    CAS  PubMed  Google Scholar 

  24. Jacobi AM, Rohde W, Ventz M, Riemekasten G, Burmester GR, Hiepe F (2001) Enhanced serum prolactin (PRL) in patients with systemic lupus erythematosus: PRL levels are related to the disease activity. Lupus 10:554–561

    Article  CAS  PubMed  Google Scholar 

  25. Leaños-Miranda A, Pascoe-Lira D, Chávez-Rueda KA, Blanco-Favela F (2001) Antiprolactin autoantibodies in systemic lupus erythematosus: frequency and correlation with prolactinemia and disease activity. J Rheumatol 28:1546–1553

    PubMed  Google Scholar 

  26. Rezaieyazdi Z, Hesamifard A (2006) Correlation between serum prolactin levels and lupus activity. Rheumatol Int 26:1036–1039

    Article  CAS  PubMed  Google Scholar 

  27. Shabanova SS, Ananieva LP, Alekberova ZS, Guzov II (2008) Ovarian function and disease activity in patients with systemic lupus erythematosus. Clin Exp Rheumatol 26:436–441

    CAS  PubMed  Google Scholar 

  28. McMurray RW, May W (2003) Sex hormones and systemic lupus erythematosus: review and meta-analysis. Arthritis Rheum 48:2100–2110

    Article  CAS  PubMed  Google Scholar 

  29. Chuang E, Molitch ME (2007) Prolactin and autoimmune diseases in humans. Acta Biomed 78(Suppl 1):255–261

    PubMed  Google Scholar 

  30. Larrea F, Martínez-Castillo A, Cabrera V et al (1997) A bioactive 60-kilodalton prolactin species is preferentially secreted in cultures of mitogen-stimulated and nonstimulated peripheral blood mononuclear cells from subjects with systemic lupus erythematosus. J Clin Endocrinol Metab 82:3664–3669

    Article  CAS  PubMed  Google Scholar 

  31. Jacobi AM, Rohde W, Volk HD, Dörner T, Burmester GR, Hiepe F (2001) Prolactin enhances the in vitro production of IgG in peripheral blood mononuclear cells from patients with systemic lupus erythematosus but not from healthy controls. Ann Rheum Dis 60:242–247

    Article  CAS  PubMed  Google Scholar 

  32. Chavez-Rueda K, Legorreta-Haquet VM, Cervera-Castillo H et al (2007) Effect of prolactin on lymphocyte activation from systemic lupus erythematosus patients. Ann N Y Acad Sci 1108:157–165

    Article  CAS  PubMed  Google Scholar 

  33. Kramer CK, Tourinho TF, de Castro WP, da Costa Oliveira M (2005) Association between systemic lupus erythematosus, rheumatoid arthritis, hyperprolactinemia and thyroid autoantibodies. Arch Med Res 36:54–58

    Article  CAS  PubMed  Google Scholar 

  34. Rastin M, Hatef MR, Tabasi N, Sheikh A, Morad Abbasi J, Mahmoudi M (2007) Sex hormones and peripheral white blood cell subsets in systemic lupus erythematosus patients. Iran J Immunol 4:110–115

    PubMed  Google Scholar 

  35. Walker SE (2001) Bromocriptine treatment of systemic lupus erythematosus. Lupus 10:762–768

    Article  CAS  PubMed  Google Scholar 

  36. Vera-Lastra O, Mendez C, Jara LJ et al (2003) Correlation of prolactin serum concentrations with clinical activity and remission in patients with systemic lupus erythematosus. Effect of conventional treatment. J Rheumatol 30:2140–2146

    CAS  PubMed  Google Scholar 

  37. Hrycek A, Pochopień-Kenig G, Scieszka J (2007) Selected acute phase proteins and interleukin-6 in systemic lupus erythematosus patients treated with low doses of quinagolide. Autoimmunity 40:217–222

    Article  CAS  PubMed  Google Scholar 

  38. Orbach H, Zandman-Goddard G, Amital H et al (2007) Novel biomarkers in autoimmune diseases: prolactin, ferritin, vitamin D, and TPA levels in autoimmune diseases. Ann N Y Acad Sci 1109:385–400

    Article  CAS  PubMed  Google Scholar 

  39. Jara LJ, Benitez G, Medina G (2008) Prolactin, dendritic cells, and systemic lupus erythematosus. Autoimmun Rev 7:251–255

    Article  CAS  PubMed  Google Scholar 

  40. Walker SE (2006) Impaired hypothalamic function, prolactinomas, and autoimmune diseases. J Rheumatol 33:1036–1037

    PubMed  Google Scholar 

  41. Méndez I, Alcocer-Varela J, Parra A et al (2004) Neuroendocrine dopaminergic regulation of prolactin release in systemic lupus erythematosus: a possible role of lymphocyte-derived prolactin. Lupus 13:45–53

    Article  PubMed  Google Scholar 

  42. La Montagna G, Baruffo A, Pasquali D, Bellastella A, Tirri G, Sinisi AA (2001) Assessment of pituitary gonadotropin release to gonadotropin releasing hormone/thyroid-stimulating hormone stimulation in women with systemic sclerosis. Rheumatology (Oxford) 40:310–314

    Article  Google Scholar 

  43. Shahin AA, Abdoh S, Abdelrazik M (2002) Prolactin and thyroid hormones in patients with systemic sclerosis: correlations with disease manifestations and activity. Z Rheumatol 61:703–709

    Article  CAS  PubMed  Google Scholar 

  44. Hilty C, Brühlmann P, Sprott H et al (2000) Altered diurnal rhythm of prolactin in systemic sclerosis. J Rheumatol 27:2160–2165

    CAS  PubMed  Google Scholar 

  45. Vera-Lastra O, Jara LJ, Medina G et al (2006) Functional hyperprolactinemia and hypophyseal microadenoma in systemic sclerosis. J Rheumatol 33:1108–1112

    PubMed  Google Scholar 

  46. Sicinska J, Olszewska M, Uhrynowska-Tyszkiewicz I, Rudnicka L (2006) Prolactin synthesis by lymphocytes from patients with systemic sclerosis. Biomed Pharmacother 60:152–155

    Article  PubMed  Google Scholar 

  47. Straub RH, Zeuner M, Lock G, Schölmerich J, Lang B (1997) High prolactin and low dehydroepiandrosterone sulphate serum levels in patients with severe systemic sclerosis. Br J Rheumatol 36:426–432

    Article  CAS  PubMed  Google Scholar 

  48. Mirone L, Barini A, Barini A (2006) Androgen and prolactin (Prl) levels in systemic sclerosis (SSc): relationship to disease severity. Ann N Y Acad Sci 1069:257–262

    Article  CAS  PubMed  Google Scholar 

  49. Berczi I, Cosby H, Hunter T, Baragar F, McNeilly AS, Friesen HG (1987) Decreased bioactivity of circulating prolactin in patients with rheumatoid arthritis. Br J Rheumatol 26:433–436

    Article  CAS  PubMed  Google Scholar 

  50. McMurray RW, Allen SH, Pepmueller PH, Keisler D, Cassidy JT (1995) Elevated serum prolactin levels in children with juvenile rheumatoid arthritis and antinuclear antibody seropositivity. J Rheumatol 22:1577–1580

    CAS  PubMed  Google Scholar 

  51. Jorgensen C, Bressot N, Bologna C, Sany J (1995) Dysregulation of the hypothalamo-pituitary axis in rheumatoid arthritis. J Rheumatol 22:1829–1833

    CAS  PubMed  Google Scholar 

  52. Templ E, Koeller M, Riedl M, Wagner O, Graninger W, Luger A (1996) Anterior pituitary function in patients with newly diagnosed rheumatoid arthritis. Br J Rheumatol 35:350–356

    Article  CAS  PubMed  Google Scholar 

  53. Eijsbouts AM, van den Hoogen FH, Laan RF, Sweep CG, Hermus AR, van de Putte LB (2005) Decreased prolactin response to hypoglycaemia in patients with rheumatoid arthritis: correlation with disease activity. Ann Rheum Dis 64:433–437

    Article  CAS  PubMed  Google Scholar 

  54. Imrich R, Vigas M, Rovensky J (2005) Different threshold for prolactin response to hypoglycaemia in patients with rheumatoid arthritis? Ann Rheum Dis 64:515–556

    Article  CAS  PubMed  Google Scholar 

  55. Nagafuchi H, Suzuki N, Kaneko A, Asai T, Sakane T (1999) Prolactin locally produced by synovium infiltrating T lymphocytes induces excessive synovial cell functions in patients with rheumatoid arthritis. J Rheumatol 26:1890–1900

    CAS  PubMed  Google Scholar 

  56. Dougados M, Duchesne L, Amor B (1998) Bromocriptine and cyclosporine A combination therapy in rheumatoid arthritis. Arthritis Rheum 31:1333–1341

    Article  Google Scholar 

  57. Gutiérrez MA, Anaya JM, Scopelitis E, Citera G, Silveira L, Espinoza LR (1994) Hyperprolactinaemia in primary Sjögren's syndrome. Ann Rheum Dis 53:425

    Article  PubMed  Google Scholar 

  58. Buskila D, Berezin M, Gur H et al (1995) Autoantibody profile in the sera of women with hyperprolactinemia. J Autoimmun 8:415–424

    Article  CAS  PubMed  Google Scholar 

  59. Haga HJ, Rygh T (1999) The prevalence of hyperprolactinemia in patients with primary Sjögren's syndrome. J Rheumatol 26:1291–1295

    CAS  PubMed  Google Scholar 

  60. El Miedany YM, Ahmed I, Moustafa H, El Baddini M (2004) Hyperprolactinemia in Sjogren's syndrome: a patient subset or a disease manifestation? Joint Bone Spine 71:203–208

    Article  PubMed  Google Scholar 

  61. Steinfeld S, Rommes S, François C et al (2000) Big prolactin 60 kDa is overexpressed in salivary glandular epithelial cells from patients with Sjögren's syndrome. Lab Invest 80:239–247

    Article  CAS  PubMed  Google Scholar 

  62. Steinfeld S, Maho A, Chaboteaux C et al (2000) Prolactin up-regulates cathepsin B and D expression in minor salivary glands of patients with Sjögren's syndrome. Lab Invest 80:1711–1720

    Article  CAS  PubMed  Google Scholar 

  63. Johnson EO, Moutsopoulos HM (2000) Neuroendocrine manifestations in Sjögren's syndrome. Relation to the neurobiology of stress. Ann N Y Acad Sci 917:797–808

    Article  CAS  PubMed  Google Scholar 

  64. Bachelot A, Binart N (2007) Reproductive role of prolactin. Reproduction 133:361–369

    Article  CAS  PubMed  Google Scholar 

  65. Murphy VE, Smith R, Giles RWB et al (2006) Endocrine regulation of human fetal growth: the role of the mother, placenta, and fetus. Endocr Rev 27:141–169

    Article  PubMed  Google Scholar 

  66. Aagard-Tillery KM, Silver R, Dalton J (2006) Immunology of normal pregnancy. Semin Fetal Neonatal Med 11:279–295

    Article  Google Scholar 

  67. Kanik KS, Wilder RL (2000) Hormonal alterations in rheumatoid arthritis, including the effects of pregnancy. Rheum Dis Clin North Am 26:805–823

    Article  CAS  PubMed  Google Scholar 

  68. Rai R, Regan L (2006) Recurrent miscarriage. Lancet 368:601–611

    Article  PubMed  Google Scholar 

  69. Clowse ME (2007) Lupus activity in pregnancy. Rheum Dis Clin North Am 33:237–252

    Article  PubMed  Google Scholar 

  70. Jara-Quezada L, Graef A, Lavalle C (1991) Prolactin and gonadal hormones during pregnancy in systemic lupus erythematosus. J Rheumatol 18:349–353

    CAS  PubMed  Google Scholar 

  71. Jara LJ, Pacheco-Reyes H, Medina G, Angeles U, Cruz-Cruz P, Saavedra MA (2007) Prolactin levels are associated with lupus activity, lupus anticoagulant, and poor outcome in pregnancy. Ann N Y Acad Sci 1108:218–226

    Article  CAS  PubMed  Google Scholar 

  72. Shoenfeld Y, Blank M (2004) Autoantibodies associated with reproductive failure. Lupus 13:643–648

    Article  CAS  PubMed  Google Scholar 

  73. Neidhart M (1996) Elevated serum prolactin or elevated prolactin/cortisol ratio are associated with autoimmune processes in systemic lupus erythematosus and other connective tissue diseases. J Rheumatol 23:476–481

    CAS  PubMed  Google Scholar 

  74. Piero E, Andreani CL, Lazzarrin N et al (1999) Effect of anticardiolipin antibodies on prolactin and insulin-like growth factor binding protein-1 production by human decidual cells. Am J Reprod Immunol 41:209–216

    Google Scholar 

  75. Francis J, Rai R, Sebire NJ et al (2006) Impaired expression of endometrial differentiation markers and complement regulatory proteins in patients with recurrent pregnancy loss associated with antiphospholipid syndrome. Mol Human Reprod 12:435–442

    Article  CAS  Google Scholar 

  76. Leaños-Miranda A, Cardenas-Mondragon G, Ulloa-Aguirre A, Isordia-Salas I, Parra A, Ramirez-Peredo J (2007) Anti-prolactin antibodies in pregnant women with systemic lupus erythematosus: maternal and fetal outcome. Lupus 16:342–349

    Article  PubMed  Google Scholar 

  77. Doria A, Cutolo M, Ghirardello A et al (2002) Steroid hormones and disease activity during pregnancy in systemic lupus erythematosus. Arthritis Rheum 47:202–209

    Article  CAS  PubMed  Google Scholar 

  78. Muñoz-Valle JF, Vázquez-Del Mercado M, García-Iglesias T et al (2003) T(H)1/T(H)2 cytokine profile, metalloprotease-9 activity and hormonal status in pregnant rheumatoid arthritis and systemic lupus erythematosus patients. Clin Exp Immunol 131:377–384

    Article  PubMed  Google Scholar 

  79. Yang XY, Liang LQ, Xu HS et al (2003) Efficacy of oral bromocriptine in protecting the postpartum systemic lupus erythematosus patients from disease relapse. Zhonghua Nei Ke Za Zhi 42:621–624

    PubMed  Google Scholar 

  80. Jara LJ, Cruz-Cruz P, Saavedra MA et al (2007) Bromocriptine during pregnancy in systemic lupus erythematosus. A pilot clinical trial. Ann N Y Acad Sci 1110:297–304

    Article  CAS  PubMed  Google Scholar 

  81. Barret JH, Brennan P, Fiddler M, Silman A (2000) Breast-feeding and postpartum relapse in women with rheumatoid and inflammatory arthritis. Arthritis Rheum 43:1010–1015

    Article  Google Scholar 

  82. Aho K, Heliövaara M (2004) Risk factors for rheumatoid arthritis. Ann Med 36:242–251

    Article  CAS  PubMed  Google Scholar 

  83. Zoli A, Lizzio MM, Ferlisi EM et al (2002) ACTH, cortical and prolactin in active rheumatoid arthritis. Clin Rheumatol 21:289–293

    Article  CAS  PubMed  Google Scholar 

  84. Jara LJ, Medina G, Navarro C, Saavedra MA, Blanco-Favela F, Espinoza LR (2008) Pregnancy, hormones and autoimmune rheumatic diseases. In: Walker S, Jara LJ (eds) Endocrine manifestations of systemic autoimmune diseases. Handbook of systemic autoimmune diseases, vol. 9. Elsevier, Amsterdam, pp 185–197

    Chapter  Google Scholar 

  85. Østensen M, Villiger PM (2007) The remission of rheumatoid arthritis during pregnancy. Semin Immunopathol 29:185–191

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Direction of Education and Research, Hospital de Especialidades Centro Médico La Raza, IMSS, Universidad Nacional Autónoma de México, Mexico City, Mexico

    Luis J. Jara

  2. Universidad Nacional Autónoma de México, Hospital de Especialidades Centro Médico La Raza, IMSS, Mexico City, Mexico

    Luis J. Jara & Olga Vera-Lastra

  3. Clinical Research Unit, Hospital de Especialidades Centro Médico La Raza, IMSS, Mexico City, Mexico

    Gabriela Medina

  4. Rheumatology Department, Hospital de Especialidades Centro Médico La Raza, IMSS, Mexico City, Mexico

    Miguel A. Saavedra

  5. Internal Medicine Department, Hospital de Especialidades Centro Médico La Raza, IMSS, Universidad Nacional Autónoma de México, Mexico City, Mexico

    Olga Vera-Lastra

  6. Instituto Nacional de Enfermedades Respiratorias, SSA, México City, Mexico

    Carmen Navarro

  7. Hospital de Especialidades Centro Médico La Raza, IMSS, Seris y Zaachila S/N, Col. La Raza, Mexico City, Mexico

    Luis J. Jara

Authors
  1. Luis J. Jara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gabriela Medina
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Miguel A. Saavedra
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Olga Vera-Lastra
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Carmen Navarro
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Luis J. Jara.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jara, L.J., Medina, G., Saavedra, M.A. et al. Prolactin and Autoimmunity. Clinic Rev Allerg Immunol 40, 50–59 (2011). https://doi.org/10.1007/s12016-009-8185-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12016-009-8185-3

Keywords

Search

Navigation