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Gene Review

Prl  -  prolactin

Mus musculus

Synonyms: AV290867, PRL, Prl1a1, Prolactin
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Disease relevance of Prl

  • A number of disease states, including the growth of different forms of cancer as well as various autoimmune diseases, appear to be related to an overproduction of PRL, which may act in an endocrine, autocrine, or paracrine manner, or via an increased sensitivity to the hormone [1].
  • A mouse model of isolated PRL deficiency (PRL-/-) was created by gene disruption in an effort to further understand the molecular basis of mammary gland development and breast cancer [2].
  • An absence of nuclear translocation of PRLR was also observed in a 293 cell line stably expressing the receptor, and in physiological targets for PRL, i.e. in Nb2 lymphoma cells expressing the Nb2 form of the receptor or in BGME mammary gland epithelial cells upon overexpression of a Flag-tagged PRLR [3].
  • We are reporting that PRL deficiency does not affect the rate of weight gain, body composition, serum lipids, or adiponectin levels in either sex on any diet [4].
  • In this report, we identify and characterize a new member of the rat PRL family, examine the impact of maternal hypoxia on placental PRL family gene expression, and investigate maternal adaptive responses to hypoxia [5].

Psychiatry related information on Prl

  • Prolactin (PRL) is the primary lactogenic pituitary hormone that plays an essential role in many aspects of reproduction, from fertilization to mammary gland development and maternal behavior [6].
  • Mice deficient in the interferon type I receptor have reduced REM sleep and altered hypothalamic hypocretin, prolactin and 2',5'-oligoadenylate synthetase expression [7].
  • We showed recently that ghrelin promotes slow-wave sleep and the nocturnal release of GH, cortisol and prolactin in humans [8].
  • Daily administration of bromocriptine, a suppressor of pituitary PRL secretion, increased the latency period and decreased the incidence of tumor development in HAN bearing mice [9].
  • 0. When secreted mouse PRL was incubated in alkaline (pH 10.0) conditions at 25 C, ammonia was released as the conversion reaction occurred [10].

High impact information on Prl


Chemical compound and disease context of Prl


Biological context of Prl


Anatomical context of Prl


Associations of Prl with chemical compounds

  • In dwarfs supplemented postnatally with dietary thyroxine for 9 wks, the treatment failed to produce immunoreactive GH, TSH or Prl cells [26].
  • We conclude that PRL inhibits lactotrophs by two distinct mechanisms: (a) indirectly by activation of hypothalamic dopamine neurons and (b) directly within the pituitary in a dopamine-independent fashion [27].
  • These results demonstrate that JAK protein tyrosine kinases couple PRL binding to tyrosine phosphorylation and proliferation [28].
  • Pregnancy, established by mating progesterone-treated PRL-/- females with PRL-/- males, led to complete morphological development of the mammary gland, appropriate to the gestational stage [2].
  • Proliferin (PLF), a protein which has homology to PRL and GH, has been implicated in the regulation of cell growth and differentiation [29].

Physical interactions of Prl


Enzymatic interactions of Prl

  • A cytosolic protein-tyrosine phosphatase PTP1B specifically dephosphorylates and deactivates prolactin-activated STAT5a and STAT5b [22].
  • We have previously shown that in HC11 mammary epithelial cells Stat5a is phosphorylated on Tyr(694) in a prolactin-sensitive manner, whereas serine phosphorylation is constitutive (Wartmann, M., Cella, N., Hofer, P., Groner, B., Xiuwen, L., Hennighausen, L., and Hynes, N. E. (1996) J. Biol. Chem. 271, 31863-31868) [34].

Regulatory relationships of Prl


Other interactions of Prl

  • We used Drd2(-/-) and Prlr(-/-) mutant mice to bypass this feedback and investigate possible dopamine-independent effects of PRL on lactotroph function [27].
  • Signals from basement membrane are transduced by beta1 integrins and are required for prolactin to activate DNA binding of the milk protein gene transcription factor, Stat5 [40].
  • We identified a gamma-interferon activation sequence (GAS) in the region between residues -965 to -725 of the RANKL promoter, which conferred a PRL response [36].
  • These results are the first demonstrations of a role for tyrosine phosphorylation of NKCC1 and of the PRL-JAK2 cascade in the regulation of Cl- transport [37].
  • In this study, we provide evidence that part of the effect of PRL on mammary gland growth is mediated by IGF-II [38].

Analytical, diagnostic and therapeutic context of Prl

  • The technique of gene targeting in mice has been used to develop the first experimental model in which the effect of the complete absence of any lactogen or PRL-mediated effects can be studied [1].
  • Progesterone Receptor Repression of Prolactin/Signal Transducer and Activator of Transcription 5-Mediated Transcription of the {beta}-Casein Gene in Mammary Epithelial Cells [41].
  • Immunofluorescence combined with detailed confocal laser microscopy showed that addition of PRL (0 to 12 hours) to COS-7, CHO and NIH-3T3 transfected fibroblasts induces rapid internalization of the receptor (long form), without any translocation to the nucleus [3].
  • METHODS: In this study, the expression of PRL in the mouse kidney was investigated by solution-phase and in situ reverse transcription-polymerase chain reaction (RT-PCR) methods and immunohistochemistry [42].
  • Trace amounts of mRNA for GlyCAM 1 were detected by RT-PCR in mammary tissue of PRL-/- mice [43].


  1. Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice. Bole-Feysot, C., Goffin, V., Edery, M., Binart, N., Kelly, P.A. Endocr. Rev. (1998) [Pubmed]
  2. Prolactin gene-disruption arrests mammary gland development and retards T-antigen-induced tumor growth. Vomachka, A.J., Pratt, S.L., Lockefeer, J.A., Horseman, N.D. Oncogene (2000) [Pubmed]
  3. Internalization of prolactin receptor and prolactin in transfected cells does not involve nuclear translocation. Perrot-Applanat, M., Gualillo, O., Buteau, H., Edery, M., Kelly, P.A. J. Cell. Sci. (1997) [Pubmed]
  4. The prolactin-deficient mouse has an unaltered metabolic phenotype. Lapensee, C.R., Horseman, N.D., Tso, P., Brandebourg, T.D., Hugo, E.R., Ben-Jonathan, N. Endocrinology (2006) [Pubmed]
  5. Prolactin-like protein-f subfamily of placental hormones/cytokines: responsiveness to maternal hypoxia. Ho-Chen, J.K., Bustamante, J.J., Soares, M.J. Endocrinology (2007) [Pubmed]
  6. Immune system development and function in prolactin receptor-deficient mice. Bouchard, B., Ormandy, C.J., Di Santo, J.P., Kelly, P.A. J. Immunol. (1999) [Pubmed]
  7. Mice deficient in the interferon type I receptor have reduced REM sleep and altered hypothalamic hypocretin, prolactin and 2',5'-oligoadenylate synthetase expression. Bohnet, S.G., Traynor, T.R., Majde, J.A., Kacsoh, B., Krueger, J.M. Brain Res. (2004) [Pubmed]
  8. Nocturnal ghrelin, ACTH, GH and cortisol secretion after sleep deprivation in humans. Schüssler, P., Uhr, M., Ising, M., Weikel, J.C., Schmid, D.A., Held, K., Mathias, S., Steiger, A. Psychoneuroendocrinology (2006) [Pubmed]
  9. Associated effects of bromocriptine on neoplastic progression of mouse mammary preneoplastic hyperplastic alveolar nodule line C4 and on hyperplastic alveolar nodule-infiltrating and splenic lymphocyte function. Tsai, S.J., Loeffler, D.A., Heppner, G.H. Cancer Res. (1992) [Pubmed]
  10. Secreted mouse prolactin (PRL) and stored ovine PRL. I. Biochemical characterization, isolation, and purification of their electrophoretic isoforms. Haro, L.S., Talamantes, F.J. Endocrinology (1985) [Pubmed]
  11. Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses. Teglund, S., McKay, C., Schuetz, E., van Deursen, J.M., Stravopodis, D., Wang, D., Brown, M., Bodner, S., Grosveld, G., Ihle, J.N. Cell (1998) [Pubmed]
  12. Expression of GHF-1 protein in mouse pituitaries correlates both temporally and spatially with the onset of growth hormone gene activity. Dollé, P., Castrillo, J.L., Theill, L.E., Deerinck, T., Ellisman, M., Karin, M. Cell (1990) [Pubmed]
  13. Mammary plasminogen activator: correlation with involution, hormonal modulation and comparison between normal and neoplastic tissue. Ossowski, L., Biegel, D., Reich, E. Cell (1979) [Pubmed]
  14. IRS-2 pathways integrate female reproduction and energy homeostasis. Burks, D.J., Font de Mora, J., Schubert, M., Withers, D.J., Myers, M.G., Towery, H.H., Altamuro, S.L., Flint, C.L., White, M.F. Nature (2000) [Pubmed]
  15. Early involvement of estrogen-induced pituitary tumor transforming gene and fibroblast growth factor expression in prolactinoma pathogenesis. Heaney, A.P., Horwitz, G.A., Wang, Z., Singson, R., Melmed, S. Nat. Med. (1999) [Pubmed]
  16. Activation of JAK2 tyrosine kinase by prolactin receptors in Nb2 cells and mouse mammary gland explants. Campbell, G.S., Argetsinger, L.S., Ihle, J.N., Kelly, P.A., Rillema, J.A., Carter-Su, C. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  17. Transgenic mice overexpressing the prolactin gene develop dramatic enlargement of the prostate gland. Wennbo, H., Kindblom, J., Isaksson, O.G., Törnell, J. Endocrinology (1997) [Pubmed]
  18. Evaluation of prolactin-like activity produced by concanavalin-A stimulated mouse splenocytes. Gala, R.R., Rillema, J.A. Life Sci. (1995) [Pubmed]
  19. Prostate hyperplasia in a transgenic mouse with prostate-specific expression of prolactin. Kindblom, J., Dillner, K., Sahlin, L., Robertson, F., Ormandy, C., Törnell, J., Wennbo, H. Endocrinology (2003) [Pubmed]
  20. Prolactin-mediated gene activation in mammary epithelial cells. Groner, B., Gouilleux, F. Curr. Opin. Genet. Dev. (1995) [Pubmed]
  21. A prolactin family paralog regulates reproductive adaptations to a physiological stressor. Ain, R., Dai, G., Dunmore, J.H., Godwin, A.R., Soares, M.J. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  22. A cytosolic protein-tyrosine phosphatase PTP1B specifically dephosphorylates and deactivates prolactin-activated STAT5a and STAT5b. Aoki, N., Matsuda, T. J. Biol. Chem. (2000) [Pubmed]
  23. Rac1 links integrin-mediated adhesion to the control of lactational differentiation in mammary epithelia. Akhtar, N., Streuli, C.H. J. Cell Biol. (2006) [Pubmed]
  24. Function of the homeodomain protein GHF1 in pituitary cell proliferation. Castrillo, J.L., Theill, L.E., Karin, M. Science (1991) [Pubmed]
  25. Growth hormone and prolactin stimulate tyrosine phosphorylation of insulin receptor substrate-1, -2, and -3, their association with p85 phosphatidylinositol 3-kinase (PI3-kinase), and concomitantly PI3-kinase activation via JAK2 kinase. Yamauchi, T., Kaburagi, Y., Ueki, K., Tsuji, Y., Stark, G.R., Kerr, I.M., Tsushima, T., Akanuma, Y., Komuro, I., Tobe, K., Yazaki, Y., Kadowaki, T. J. Biol. Chem. (1998) [Pubmed]
  26. Immunocytochemical effects of thyroxine stimulation on the adenohypophysis of dwarf (dw) mutant mice. Wilson, D.B., Wyatt, D.P. Cell Tissue Res. (1993) [Pubmed]
  27. Lack of prolactin receptor signaling in mice results in lactotroph proliferation and prolactinomas by dopamine-dependent and -independent mechanisms. Schuff, K.G., Hentges, S.T., Kelly, M.A., Binart, N., Kelly, P.A., Iuvone, P.M., Asa, S.L., Low, M.J. J. Clin. Invest. (2002) [Pubmed]
  28. Identification of JAK protein tyrosine kinases as signaling molecules for prolactin. Functional analysis of prolactin receptor and prolactin-erythropoietin receptor chimera expressed in lymphoid cells. Dusanter-Fourt, I., Muller, O., Ziemiecki, A., Mayeux, P., Drucker, B., Djiane, J., Wilks, A., Harpur, A.G., Fischer, S., Gisselbrecht, S. EMBO J. (1994) [Pubmed]
  29. Proliferin, a prolactin/growth hormone-like peptide represses myogenic-specific transcription by the suppression of an essential serum response factor-like DNA-binding activity. Muscat, G.E., Gobius, K., Emery, J. Mol. Endocrinol. (1991) [Pubmed]
  30. Prolactin concurrently activates src-PLD and JAK/Stat signaling pathways to induce proliferation while promoting differentiation in embryonic astrocytes. Mangoura, D., Pelletiere, C., Leung, S., Sakellaridis, N., Wang, D.X. Int. J. Dev. Neurosci. (2000) [Pubmed]
  31. Characterization of plasma and intracellular membrane prolactin receptor in lactating mouse mammary cells. Sakai, S., Mizoguchi, Y., Kim, J.Y. Endocr. J. (1994) [Pubmed]
  32. Prolactin-dependent activation of a tyrosine phosphorylated DNA binding factor in mouse mammary epithelial cells. Welte, T., Garimorth, K., Philipp, S., Doppler, W. Mol. Endocrinol. (1994) [Pubmed]
  33. Regulation of estrogen receptor activation of the prolactin enhancer/promoter by antagonistic activation function-2-interacting proteins. Schaufele, F. Mol. Endocrinol. (1999) [Pubmed]
  34. Stat5a serine phosphorylation. Serine 779 is constitutively phosphorylated in the mammary gland, and serine 725 phosphorylation influences prolactin-stimulated in vitro DNA binding activity. Beuvink, I., Hess, D., Flotow, H., Hofsteenge, J., Groner, B., Hynes, N.E. J. Biol. Chem. (2000) [Pubmed]
  35. Cloning and expression of Stat5 and an additional homologue (Stat5b) involved in prolactin signal transduction in mouse mammary tissue. Liu, X., Robinson, G.W., Gouilleux, F., Groner, B., Hennighausen, L. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  36. Receptor activator of NF-kappaB ligand induction via Jak2 and Stat5a in mammary epithelial cells. Srivastava, S., Matsuda, M., Hou, Z., Bailey, J.P., Kitazawa, R., Herbst, M.P., Horseman, N.D. J. Biol. Chem. (2003) [Pubmed]
  37. Janus kinase 2 (JAK2) regulates prolactin-mediated chloride transport in mouse mammary epithelial cells through tyrosine phosphorylation of Na+-K+-2Cl- cotransporter. Selvaraj, N.G., Omi, E., Gibori, G., Rao, M.C. Mol. Endocrinol. (2000) [Pubmed]
  38. Local insulin-like growth factor-II mediates prolactin-induced mammary gland development. Hovey, R.C., Harris, J., Hadsell, D.L., Lee, A.V., Ormandy, C.J., Vonderhaar, B.K. Mol. Endocrinol. (2003) [Pubmed]
  39. Prolactin signaling through the short form of its receptor represses forkhead transcription factor FOXO3 and its target gene galt causing a severe ovarian defect. Halperin, J., Devi, S.Y., Elizur, S., Stocco, C., Shehu, A., Rebourcet, D., Unterman, T.G., Leslie, N.D., Le, J., Binart, N., Gibori, G. Mol. Endocrinol. (2008) [Pubmed]
  40. Regulation of mammary differentiation by extracellular matrix involves protein-tyrosine phosphatases. Edwards, G.M., Wilford, F.H., Liu, X., Hennighausen, L., Djiane, J., Streuli, C.H. J. Biol. Chem. (1998) [Pubmed]
  41. Progesterone Receptor Repression of Prolactin/Signal Transducer and Activator of Transcription 5-Mediated Transcription of the {beta}-Casein Gene in Mammary Epithelial Cells. Buser, A.C., Gass-Handel, E.K., Wyszomierski, S.L., Doppler, W., Leonhardt, S.A., Schaack, J., Rosen, J.M., Watkin, H., Anderson, S.M., Edwards, D.P. Mol. Endocrinol. (2007) [Pubmed]
  42. The prolactin gene is expressed in the mouse kidney. Sakai, Y., Hiraoka, Y., Ogawa, M., Takeuchi, Y., Aiso, S. Kidney Int. (1999) [Pubmed]
  43. Glycosylation-dependent cell adhesion molecule 1 (GlyCAM 1) is induced by prolactin and suppressed by progesterone in mammary epithelium. Hou, Z., Bailey, J.P., Vomachka, A.J., Matsuda, M., Lockefeer, J.A., Horseman, N.D. Endocrinology (2000) [Pubmed]
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