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Gene Review

PRL  -  prolactin

Homo sapiens

Synonyms: Prolactin
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Disease relevance of PRL

  • Such compounds are thus candidates to counteract the undesired actions of PRL, not only in tumors, but also in dopamine-resistant prolactinomas [1].
  • There is a large body of literature showing that prolactin (PRL) exerts growth-promoting activities in breast cancer, and possibly in prostate cancer and prostate hyperplasia [1].
  • PRL- and ACTH-secreting pituitary adenomas cannot be visualized, but clinically nonfunctioning pituitary adenomas are visualized in 75% of cases with 111In-DTPA-octreotide [2].
  • When dopamine (0.01-0.1 microM) or bromocriptine (0.01-0.1 microM) was added to the culture media, a significant inhibition of GH and PRL secretion from adenoma cells from acromegalic patients was observed [3].
  • In contrast, the PRL responses of patients with weight loss exceeding 10 lb were significantly greater than those of either controls or the other depressed patients [4].

Psychiatry related information on PRL

  • The PRL response was greater in patients with affective disorders [5].
  • Both the information obtained from a review of the literature on the influence of stress on PRL secretion and our own results strongly suggest that contrary to common opinion, there is no evidence at all that psychological stress affects PRL secretion in man [6].
  • The TSH and PRL responses were compared with those obtained in a group of control patients without a history of alcohol abuse [7].
  • Sleep-related PRL release was less than normal in women with narcolepsy, with or without sleep apnea [8].
  • In contrast, MPOA infusions of the control hormone, wild-type human PRL, in Exp 3 did not delay the onset of maternal behavior [9].

High impact information on PRL


Chemical compound and disease context of PRL


Biological context of PRL

  • Several potential components of the signal transduction pathways have been identified, but as yet none has clearly been shown to be able to mimic the effect of PRL or GH [18].
  • No single second messenger mediating the action of either PRL or GH has been identified [18].
  • An assay has been developed to measure the functional activity of different forms of PRL receptor by cotransfecting a milk protein fusion gene specific to PRL coupled to a reporter-gene along with the cDNA of the PRL receptor [18].
  • Human growth hormone (hGH) elicits a diverse set of biological activities including lactation that derives from binding to the prolactin (PRL) receptor [19].
  • The mean ocntent of PRL in the pituitary gland increased sharply from 14.8 plus or minus 4.6 ng at 15-19 wk to 405 plus or minus 142 ng at 20-24 wk and 542 plus or minus ng at 25-29 wk gestation [20].

Anatomical context of PRL

  • Since PRL has been implicated in T cell function and human GH can interact with the PRL receptor, DW/J dwarf mice were treated with either ovine GH (ovGH) (20 micrograms/d) or ovine PRL (ovPRL) (20 micrograms/d) [21].
  • The PRL-binding protein has a very high affinity for the hormone, almost 10 times higher than the affinity of the mammary gland membrane receptor [22].
  • Furthermore, PRL receptors were demonstrated on four cell lines of human and mouse origin [23].
  • At concentrations of CsA from 10(-10) through 10(-8) M, the amount of PRL bound to MNC markedly increased to ca. 400% of controls, whereas CsA concentrations of 10(-6) and 10(-5) M totally inhibited PRL binding to lymphocytes [23].
  • Finally, PRL receptors were identified on purified populations of T and B lymphocytes isolated from human spleens, and CsA again inhibited PRL binding at concentrations of 10(-7) and 10(-6) M [23].

Associations of PRL with chemical compounds

  • Because dopamine analogs are unable to inhibit PRL production in extrapituitary sites, alternative strategies need investigation [1].
  • Several lines of evidence support the view that high plasma estrogen levels characteristic of gestation act directly on the fetal anterior hypophysis to stimulate PRL secretion or to sensitize the secretory mechanism of the lactotrope, increasing its responsiveness to other stimuli [20].
  • Norepinephrine, likewise, caused a suppression of PRL secretion from adenomatous and nonadenomatous pituitary cells [3].
  • The values for PRL, GH, and TSH at baseline and after protirelin stimulation were normal [24].
  • The increases in plasma levels of prolactin (PRL) and growth hormone (GH) following intravenous administration of the 5-hydroxytryptamine precursor tryptophan (100 mg/kg) were assessed in 30 depressed patients and 30 control subjects [4].
  • Insulin suppressed PRL expression and release from differentiated adipocytes but moderately stimulated PRL release from nondifferentiated cells [25].
  • Premenopausal mean nighttime PRL (P = 0.026) and cortisol (P = 0.018) were higher during EPT compared with placebo [26].

Physical interactions of PRL

  • This hPRL variant binds one-sixth as strongly as wild-type hGH, but shares only 26 percent overall sequence identity with hGH [27].
  • However, prolactin was effectively inhibited only by compounds preferentially bound to SSTR2 (20-30%, P < 0.05) [28].
  • Disruption of Stat binding to the distal GAS site destroys PRL-induced promoter activity, whereas disruption of the proximal site has no effect [29].
  • Decidualized human endometrial stromal cells transfected with 3 kb of the extrapituitary PRL (exon 1a) promoter coupled to a luciferase expression vector responded to IL-2 (10 ng/mL) with a significant decrease in luciferase activity [30].
  • EGF stimulation is mediated by increased synthesis of c-fos and c-jun, resulting in AP-1 binding to the proximal hPRL pituitary promoter [31].

Enzymatic interactions of PRL


Co-localisations of PRL


Regulatory relationships of PRL


Other interactions of PRL

  • PRL and GH are hormones with a wide spectrum of actions [18].
  • Therefore, hPRL is the preferred ligand for the assessment of prolactin receptor levels in human breast cancer biopsy specimens [41].
  • Thus, somatostatin analogues with improved selective binding affinity for these receptor subtypes may be effective in the treatment of either GH- or PRL-secreting adenomas [36].
  • In contrast, suppression of prolactin is mediated mainly by SSTR2 [28].
  • Despite significant mutual use of Stats by IFNs and PRL, these results indicated a high degree of signaling specificity in the two receptor systems, and that cytoplasmic levels of Stat proteins were not limiting [37].

Analytical, diagnostic and therapeutic context of PRL


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  2. Octreotide and related somatostatin analogs in the diagnosis and treatment of pituitary disease and somatostatin receptor scintigraphy. Lamberts, S.W., Hofland, L.J., de Herder, W.W., Kwekkeboom, D.J., Reubi, J.C., Krenning, E.P. Frontiers in neuroendocrinology. (1993) [Pubmed]
  3. Direct effects of catecholamines, thyrotropin-releasing hormone, and somatostatin on growth hormone and prolactin secretion from adenomatous and nonadenomatous human pituitary cells in culture. Ishibashi, M., Yamaji, T. J. Clin. Invest. (1984) [Pubmed]
  4. Neuroendocrine responses to intravenous tryptophan in major depression. Cowen, P.J., Charig, E.M. Arch. Gen. Psychiatry (1987) [Pubmed]
  5. Growth hormone and prolactin response to apomorphine in schizophrenia and the major affective disorders. Relation to duration of illness and depressive symptoms. Meltzer, H.Y., Kolakowska, T., Fang, V.S., Fogg, L., Robertson, A., Lewine, R., Strahilevitz, M., Busch, D. Arch. Gen. Psychiatry (1984) [Pubmed]
  6. Prolactin in patients with major depressive disorder and in healthy subjects. III. Investigation of basal and post-TRH prolactin during different forms of acute and chronic psychological stress. Baumgartner, A., Gräf, K.J., Kürten, I. Biol. Psychiatry (1988) [Pubmed]
  7. Prolactin and thyrotropin responses to thyrotropin-releasing hormone and metoclopramide in men with chronic alcoholism. Röjdmark, S., Adner, N., Andersson, D.E., Austern, J., Lamminpää, K. J. Clin. Endocrinol. Metab. (1984) [Pubmed]
  8. Disordered growth hormone and prolactin secretion in primary disorders of sleep. Clark, R.W., Schmidt, H.S., Malarkey, W.B. Neurology (1979) [Pubmed]
  9. Central infusions of the recombinant human prolactin receptor antagonist, S179D-PRL, delay the onset of maternal behavior in steroid-primed, nulliparous female rats. Bridges, R., Rigero, B., Byrnes, E., Yang, L., Walker, A. Endocrinology (2001) [Pubmed]
  10. Neuroendocrine-immune system interactions and autoimmunity. Wilder, R.L. Annu. Rev. Immunol. (1995) [Pubmed]
  11. Pituitary tumors: diagnosis and therapy. Cook, D.M. CA: a cancer journal for clinicians. (1983) [Pubmed]
  12. Mechanisms controlling the function and life span of the corpus luteum. Niswender, G.D., Juengel, J.L., Silva, P.J., Rollyson, M.K., McIntush, E.W. Physiol. Rev. (2000) [Pubmed]
  13. Prolactin: structure, function, and regulation of secretion. Freeman, M.E., Kanyicska, B., Lerant, A., Nagy, G. Physiol. Rev. (2000) [Pubmed]
  14. Functional role of estrogen in pituitary tumor pathogenesis. Heaney, A.P., Fernando, M., Melmed, S. J. Clin. Invest. (2002) [Pubmed]
  15. Synergistic action of prolactin (PRL) and androgen on PRL-inducible protein gene expression in human breast cancer cells: a unique model for functional cooperation between signal transducer and activator of transcription-5 and androgen receptor. Carsol, J.L., Gingras, S., Simard, J. Mol. Endocrinol. (2002) [Pubmed]
  16. Effects of disodium EDTA and calcium infusion on prolactin and thyrotropin responses to thyrotropin-releasing hormone in healthy man. Dudczak, R., Waldhäusl, W.K., Bratusch-Marrain, P. J. Clin. Endocrinol. Metab. (1983) [Pubmed]
  17. Coexpression and cross-regulation of the prolactin receptor and sex steroid hormone receptors in breast cancer. Ormandy, C.J., Hall, R.E., Manning, D.L., Robertson, J.F., Blamey, R.W., Kelly, P.A., Nicholson, R.I., Sutherland, R.L. J. Clin. Endocrinol. Metab. (1997) [Pubmed]
  18. The prolactin/growth hormone receptor family. Kelly, P.A., Djiane, J., Postel-Vinay, M.C., Edery, M. Endocr. Rev. (1991) [Pubmed]
  19. Zinc mediation of the binding of human growth hormone to the human prolactin receptor. Cunningham, B.C., Bass, S., Fuh, G., Wells, J.A. Science (1990) [Pubmed]
  20. The ontogenesis of human fetal hormones. III. Prolactin. Aubert, M.J., Grumbach, M.M., Kaplan, S.L. J. Clin. Invest. (1975) [Pubmed]
  21. Differential effects of growth hormone and prolactin on murine T cell development and function. Murphy, W.J., Durum, S.K., Longo, D.L. J. Exp. Med. (1993) [Pubmed]
  22. Identification of prolactin and growth hormone binding proteins in rabbit milk. Postel-Vinay, M.C., Belair, L., Kayser, C., Kelly, P.A., Djiane, J. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  23. Prolactin receptors on human T and B lymphocytes: antagonism of prolactin binding by cyclosporine. Russell, D.H., Kibler, R., Matrisian, L., Larson, D.F., Poulos, B., Magun, B.E. J. Immunol. (1985) [Pubmed]
  24. Behavioral and endocrine responses of schizophrenic patients to TRH (protirelin). Prange, A.J., Loosen, P.T., Wilson, I.C., Meltzer, H.Y., Fang, V.S. Arch. Gen. Psychiatry (1979) [Pubmed]
  25. Prolactin release by adipose explants, primary adipocytes, and LS14 adipocytes. Hugo, E.R., Borcherding, D.C., Gersin, K.S., Loftus, J., Ben-Jonathan, N. J. Clin. Endocrinol. Metab. (2008) [Pubmed]
  26. 24-hour serum levels of growth hormone, prolactin, and cortisol in pre- and postmenopausal women: the effect of combined estrogen and progestin treatment. Kalleinen, N., Polo-Kantola, P., Irjala, K., Porkka-Heiskanen, T., Vahlberg, T., Virkki, A., Polo, O. J. Clin. Endocrinol. Metab. (2008) [Pubmed]
  27. Engineering human prolactin to bind to the human growth hormone receptor. Cunningham, B.C., Henner, D.J., Wells, J.A. Science (1990) [Pubmed]
  28. Somatostatin receptor subtype specificity in human fetal pituitary cultures. Differential role of SSTR2 and SSTR5 for growth hormone, thyroid-stimulating hormone, and prolactin regulation. Shimon, I., Taylor, J.E., Dong, J.Z., Bitonte, R.A., Kim, S., Morgan, B., Coy, D.H., Culler, M.D., Melmed, S. J. Clin. Invest. (1997) [Pubmed]
  29. PRL activates the cyclin D1 promoter via the Jak2/Stat pathway. Brockman, J.L., Schroeder, M.D., Schuler, L.A. Mol. Endocrinol. (2002) [Pubmed]
  30. Interleukin-2 inhibits the synthesis and release of prolactin from human decidual cells. Kanda, Y., Jikihara, H., Markoff, E., Handwerger, S. J. Clin. Endocrinol. Metab. (1999) [Pubmed]
  31. EGF stimulates Pit-1 independent transcription of the human prolactin pituitary promoter in human breast cancer SK-BR-3 cells through its proximal AP-1 response element. Manfroid, I., Van de Weerdt, C., Baudhuin, A., Martial, J.A., Muller, M. Mol. Cell. Endocrinol. (2005) [Pubmed]
  32. Dissociation of Janus kinase 2 and signal transducer and activator of transcription 5 activation after treatment of Nb2 cells with a molecular mimic of phosphorylated prolactin. Coss, D., Kuo, C.B., Yang, L., Ingleton, P., Luben, R., Walker, A.M. Endocrinology (1999) [Pubmed]
  33. Multiple stat complexes interact at the interferon regulatory factor-1 interferon-gamma activation sequence in prolactin-stimulated Nb2 T cells. Wang, Y.F., Yu-Lee, L.Y. Mol. Cell. Endocrinol. (1996) [Pubmed]
  34. Expression of Pit-1 and estrogen receptor messenger RNA in prolactin-producing pituitary adenomas. Sanno, N., Teramoto, A., Matsuno, A., Takekoshi, S., Itoh, J., Osamura, R.Y. Mod. Pathol. (1996) [Pubmed]
  35. Characterization of a tissue kallikrein in human prolactin-secreting adenomas. Jones, T.H., Figueroa, C.D., Smith, C., Cullen, D.R., Bhoola, K.D. J. Endocrinol. (1990) [Pubmed]
  36. Somatostatin receptor (SSTR) subtype-selective analogues differentially suppress in vitro growth hormone and prolactin in human pituitary adenomas. Novel potential therapy for functional pituitary tumors. Shimon, I., Yan, X., Taylor, J.E., Weiss, M.H., Culler, M.D., Melmed, S. J. Clin. Invest. (1997) [Pubmed]
  37. Prolactin activates Stat1 but does not antagonize Stat1 activation and growth inhibition by type I interferons in human breast cancer cells. Schaber, J.D., Fang, H., Xu, J., Grimley, P.M., Rui, H. Cancer Res. (1998) [Pubmed]
  38. Growth hormone is a human macrophage activating factor. Priming of human monocytes for enhanced release of H2O2. Warwick-Davies, J., Lowrie, D.B., Cole, P.J. J. Immunol. (1995) [Pubmed]
  39. Prolactin receptor triggering. Evidence for rapid tyrosine kinase activation. Rui, H., Djeu, J.Y., Evans, G.A., Kelly, P.A., Farrar, W.L. J. Biol. Chem. (1992) [Pubmed]
  40. Stat5 activation inhibits prolactin-induced AP-1 activity: distinct prolactin-initiated signals in tumorigenesis dependent on cell context. Gutzman, J.H., Rugowski, D.E., Nikolai, S.E., Schuler, L.A. Oncogene (2007) [Pubmed]
  41. Prolactin receptors in human breast tumors. Turcot-Lemay, L., Kelly, P.A. J. Natl. Cancer Inst. (1982) [Pubmed]
  42. G120R, a human growth hormone antagonist, shows zinc-dependent agonist and antagonist activity on Nb2 cells. Dattani, M.T., Hindmarsh, P.C., Brook, C.G., Robinson, I.C., Kopchick, J.J., Marshall, N.J. J. Biol. Chem. (1995) [Pubmed]
  43. Human scalp hair follicles are both a target and a source of prolactin, which serves as an autocrine and/or paracrine promoter of apoptosis-driven hair follicle regression. Foitzik, K., Krause, K., Conrad, F., Nakamura, M., Funk, W., Paus, R. Am. J. Pathol. (2006) [Pubmed]
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