Prolactin receptor

The prolactin receptor (PRLR) is a type I cytokine receptor[1] encoded in humans by the PRLR gene on chromosome 5p13-14. It is the receptor for prolactin (PRL). The PRLR can also bind to and be activated by growth hormone (GH) and human placental lactogen (hPL). The PRLR is expressed in the mammary glands, pituitary gland, and other tissues. It plays an important role in lobuloalveolar development of the mammary glands during pregnancy and in lactation.

Prolactin Receptor
Identifiers
SymbolPRLR
NCBI gene5618
HGNC9446
OMIM176761
PDB1RW5
RefSeqNM_000949
UniProtP16471
Other data
LocusChr. 5 p13-p12

Structure

The PRLR is a transmembrane receptor. Thus, the receptor contains an extracellular region to bind PRL, a transmembrane region, and a cytoplasmatic region.

Signaling

The PRLR is a cytokine receptor[2] and second messenger cascades include the JAK-STAT pathway, JAK-RUSH pathway,[3][4] Ras-Raf-MAPK, and PI3K/AKT/mTOR pathway.[5]

Function

Expression of the PRLR protein is found within cells of the mammary glands[6] in accordance with its role in lactation, but also is the subject of attention for its diverse and emerging roles by its expression in adipose tissue,[7] pancreatic islet cell proliferation,[8] and immune responses.[9] The PRLR has been found to be essential for lobuloalveolar maturation of the mammary glands during pregnancy, as evidenced by the fact that PRLR knockout mice show severely impaired development of lobuloalveolar structures.[10][11] Disruption of PRLR signaling pathways have been linked to tumorigenesis and breast cancer development.[12]

Ligands

Agonists

Antagonists

Prolactin receptor antagonists such as Del1-9-G129R-hPRL have been developed.[14][15][16][17][18]

See also

References
  1. Brooks CL (August 2012). "Molecular mechanisms of prolactin and its receptor". review. Endocrine Reviews. 33 (4): 504–25. doi:10.1210/er.2011-1040. PMC 3410225. PMID 22577091.
  2. Trott JF, Schennink A, Petrie WK, Manjarin R, VanKlompenberg MK, Hovey RC (May 2012). "Triennial Lactation Symposium: Prolactin: The multifaceted potentiator of mammary growth and function". Journal of Animal Science. 90 (5): 1674–86. doi:10.2527/jas.2011-4682. PMID 22205663.
  3. Helmer RA, Panchoo M, Dertien JS, Bhakta SM, Hewetson A, Chilton BS (August 2010). "Prolactin-induced Jak2 phosphorylation of RUSH: a key element in Jak/RUSH signaling". Molecular and Cellular Endocrinology. 325 (1–2): 143–9. doi:10.1016/j.mce.2010.05.010. PMC 2902710. PMID 20562009.
  4. Helmer RA, Dertien JS, Chilton BS (May 2011). "Prolactin induces Jak2 phosphorylation of RUSHY195". Molecular and Cellular Endocrinology. 338 (1–2): 79–83. doi:10.1016/j.mce.2011.03.009. PMID 21457752. S2CID 36530259.
  5. Clevenger CV, Furth PA, Hankinson SE, Schuler LA (February 2003). "The role of prolactin in mammary carcinoma". Endocrine Reviews. 24 (1): 1–27. doi:10.1210/er.2001-0036. PMC 1698952. PMID 12588805.
  6. Baran N, Kelly PA, Binart N (April 2002). "Characterization of a prolactin-regulated gene in reproductive tissues using the prolactin receptor knockout mouse model". primary. Biology of Reproduction. 66 (4): 1210–8. doi:10.1095/biolreprod66.4.1210. PMID 11906943.
  7. Viengchareun S, Servel N, Fève B, Freemark M, Lombès M, Binart N (February 2008). "Prolactin receptor signaling is essential for perinatal brown adipocyte function: a role for insulin-like growth factor-2". primary. PLOS ONE. 3 (2): e1535. doi:10.1371/journal.pone.0001535. PMC 2212135. PMID 18253483.
  8. Arumugam R, Fleenor D, Freemark M (August 2014). "Knockdown of prolactin receptors in a pancreatic beta cell line: effects on DNA synthesis, apoptosis, and gene expression". primary. Endocrine. 46 (3): 568–76. doi:10.1007/s12020-013-0073-1. PMC 3984618. PMID 24114406.
  9. Dogusan Z, Book ML, Verdood P, Yu-Lee LY, Hooghe-Peters EL (September 2000). "Prolactin activates interferon regulatory factor-1 expression in normal lympho-hemopoietic cells". primary. European Cytokine Network. 11 (3): 435–42. PMID 11022129.
  10. Horseman ND (6 December 2012). Prolactin. Springer Science & Business Media. pp. 227–. ISBN 978-1-4615-1683-5.
  11. Bland KI, Copeland EM (9 September 2009). The Breast: Comprehensive Management of Benign and Malignant Diseases. Elsevier Health Sciences. pp. 44–45. ISBN 978-1-4377-1121-9.
  12. Z. Nouhi, N. Chughtai, S. Hartley, E. Cocolakis, J.J. Lebrun, S. Ali. Defining the role of prolactin as an invasion suppressor hormone in breast cancer cells. Cancer Res, 66 (2006), pp. 1824-1832
  13. Bernichtein S, Kinet S, Jeay S, Llovera M, Madern D, Martial JA, Kelly PA, Goffin V (September 2001). "S179D-human PRL, a pseudophosphorylated human PRL analog, is an agonist and not an antagonist". Endocrinology. 142 (9): 3950–63. doi:10.1210/endo.142.9.8369. PMID 11517174.
  14. Goffin V, Touraine P, Culler MD, Kelly PA (October 2006). "Drug Insight: prolactin-receptor antagonists, a novel approach to treatment of unresolved systemic and local hyperprolactinemia?". Nat Clin Pract Endocrinol Metab. 2 (10): 571–81. doi:10.1038/ncpendmet0270. PMID 17024156.
  15. Jomain JB, Tallet E, Broutin I, Hoos S, van Agthoven J, Ducruix A, Kelly PA, Kragelund BB, England P, Goffin V (November 2007). "Structural and thermodynamic bases for the design of pure prolactin receptor antagonists: X-ray structure of Del1-9-G129R-hPRL". J Biol Chem. 282 (45): 33118–31. doi:10.1074/jbc.M704364200. PMID 17785459.
  16. Jacobson EM, Hugo ER, Tuttle TR, Papoian R, Ben-Jonathan N (November 2010). "Unexploited therapies in breast and prostate cancer: blockade of the prolactin receptor". Trends Endocrinol Metab. 21 (11): 691–8. doi:10.1016/j.tem.2010.08.004. PMC 2967606. PMID 20846877.
  17. Hansen MJ, Olsen JG, Bernichtein S, O'Shea C, Sigurskjold BW, Goffin V, Kragelund BB (2011). "Development of prolactin receptor antagonists with reduced pH-dependence of receptor binding". J Mol Recognit. 24 (4): 533–47. doi:10.1002/jmr.1064. PMID 20842635.
  18. Ferraris J, Bernichtein S, Pisera D, Goffin V (2013). "Use of prolactin receptor antagonist to better understand prolactin regulation of pituitary homeostasis". Neuroendocrinology. 98 (3): 171–9. doi:10.1159/000354701. PMID 23969780.


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