prolactin receptors

Summary

Summary: Labile proteins on or in prolactin-sensitive cells that bind prolactin initiating the cells' physiological response to that hormone. Mammary casein synthesis is one of the responses. The receptors are also found in placenta, liver, testes, kidneys, ovaries, and other organs and bind and respond to certain other hormones and their analogs and antagonists. This receptor is related to the growth hormone receptor.

Top Publications

  1. Huang X, Jiao B, Fung C, Zhang Y, Ho W, Chan C, et al. The presence of two distinct prolactin receptors in seabream with different tissue distribution patterns, signal transduction pathways and regulation of gene expression by steroid hormones. J Endocrinol. 2007;194:373-92 pubmed
    Two prolactin receptors (PRLRs) encoded by two different genes were identified in the fugu and zebrafish genomes but not in the genomes of other vertebrates...
  2. García Martínez J, Calcabrini A, Gonzalez L, Martín Forero E, Agulló Ortuño M, Simon V, et al. A non-catalytic function of the Src family tyrosine kinases controls prolactin-induced Jak2 signaling. Cell Signal. 2010;22:415-26 pubmed publisher
    ..Finally, Jak2/Stat5 pathway is also reduced in Src-/- mice mammary glands. We thus conclude that, in addition to Akt and p70S6K, SFK regulate PRLR-induced Jak2 signaling through a kinase-independent mechanism. ..
  3. Corbacho A, Macotela Y, Nava G, Eiserich J, Cross C, Martinez de la Escalera G, et al. Cytokine induction of prolactin receptors mediates prolactin inhibition of nitric oxide synthesis in pulmonary fibroblasts. FEBS Lett. 2003;544:171-5 pubmed
    ..These results reveal previously unrecognized mechanisms by which PRL and PRL receptors may play significant modulatory roles during immune-inflammatory processes. ..
  4. Binart N, Imbert Bollore P, Baran N, Viglietta C, Kelly P. A short form of the prolactin (PRL) receptor is able to rescue mammopoiesis in heterozygous PRL receptor mice. Mol Endocrinol. 2003;17:1066-74 pubmed
  5. Gutzman J, Miller K, Schuler L. Endogenous human prolactin and not exogenous human prolactin induces estrogen receptor alpha and prolactin receptor expression and increases estrogen responsiveness in breast cancer cells. J Steroid Biochem Mol Biol. 2004;88:69-77 pubmed
    ..This model will allow investigation of endogenous hPRL in mammary epithelial cells and will enable further dissection of PRL effects on other hormone signaling pathways to determine the role of PRL in breast cancer. ..
  6. Amaral M, Cunha D, Anhê G, Ueno M, Carneiro E, Velloso L, et al. Participation of prolactin receptors and phosphatidylinositol 3-kinase and MAP kinase pathways in the increase in pancreatic islet mass and sensitivity to glucose during pregnancy. J Endocrinol. 2004;183:469-76 pubmed
    ..These findings indicate that these pathways participate in the increase in islet mass and the sensitivity to glucose during pregnancy. ..
  7. Pearce S, Budge H, Mostyn A, Genever E, Webb R, Ingleton P, et al. Prolactin, the prolactin receptor and uncoupling protein abundance and function in adipose tissue during development in young sheep. J Endocrinol. 2005;184:351-9 pubmed
    ..In conclusion, we have demonstrated a close relationship between the ontogeny of UCP1 and the PRLR. Exogenous PRL administration elicits a thermogenic effect suggesting an important role for the PRLR in regulating UCP1 function. ..
  8. Zinger M, McFarland M, Ben Jonathan N. Prolactin expression and secretion by human breast glandular and adipose tissue explants. J Clin Endocrinol Metab. 2003;88:689-96 pubmed
    ..These data suggest an autocrine/paracrine role for PRL in human glandular and adipose breast tissue. ..
  9. Ben Jonathan N, Liby K, McFarland M, Zinger M. Prolactin as an autocrine/paracrine growth factor in human cancer. Trends Endocrinol Metab. 2002;13:245-50 pubmed
    ..Establishment of PRL as an active participant in tumorigenesis should inspire the development of novel therapies aimed at reducing tumor growth by suppressing PRL production or by blocking its receptors. ..

More Information

Publications62

  1. Vaclavicek A, Hemminki K, Bartram C, Wagner K, Wappenschmidt B, Meindl A, et al. Association of prolactin and its receptor gene regions with familial breast cancer. J Clin Endocrinol Metab. 2006;91:1513-9 pubmed
    ..15; P = 0.007). Genetic variation in the PRL and PRLR genes was shown to influence BC risk. Additional studies are needed to further clarify the role of the PRL and PRLR genes in the risk of BC. ..
  2. Bogorad R, Ostroukhova T, Orlova A, Rubtsov P, Smirnova O. Long isoform of prolactin receptor predominates in rat intrahepatic bile ducts and further increases under obstructive cholestasis. J Endocrinol. 2006;188:345-54 pubmed
    ..From these data, the actions of prolactin on liver are anticipated to exhibit strong cell-type specificity in both normal and pathological conditions. ..
  3. Fleenor D, Arumugam R, Freemark M. Growth hormone and prolactin receptors in adipogenesis: STAT-5 activation, suppressors of cytokine signaling, and regulation of insulin-like growth factor I. Horm Res. 2006;66:101-10 pubmed
    ..These observations suggest that somatogens and lactogens regulate adipocyte development and fat metabolism through distinct but overlapping cellular mechanisms. ..
  4. Flint D, Binart N, Boumard S, Kopchick J, Kelly P. Developmental aspects of adipose tissue in GH receptor and prolactin receptor gene disrupted mice: site-specific effects upon proliferation, differentiation and hormone sensitivity. J Endocrinol. 2006;191:101-11 pubmed
    ..Our results provide in vivo evidence that both GH and PRL stimulate differentiation of adipocytes but that the effects of GH are site specific and induce intrinsic changes in the precursor population, which are retained in vitro. ..
  5. Kloehn S, Otte C, Korsanke M, Arendt T, Clemens A, Glasow A, et al. Expression and distribution of the prolactin receptor in normal rat liver and in experimental liver cirrhosis. Horm Metab Res. 2001;33:394-401 pubmed
    ..We conclude that PRLR is distributed in normal rat liver in a typical pattern which is lost with increasing fibrosis. PRL is not produced by rat liver, indicating that PRL does not act through autocrine or paracrine mechanisms. ..
  6. Ben Jonathan N, LaPensee C, LaPensee E. What can we learn from rodents about prolactin in humans?. Endocr Rev. 2008;29:1-41 pubmed
  7. Hu Z, Zhuang L, Meng J, Tsai Morris C, Dufau M. Complex 5' genomic structure of the human prolactin receptor: multiple alternative exons 1 and promoter utilization. Endocrinology. 2002;143:2139-42 pubmed
    ..The complex promoter control system that governs transcription of the hPRLR in multiple tissues is of relevance for studies on the regulation of PRLR expression in physiological and pathological states. ..
  8. Lin C, Ponsuksili S, Tholen E, Jennen D, Schellander K, Wimmers K. Candidate gene markers for sperm quality and fertility of boar. Anim Reprod Sci. 2006;92:349-63 pubmed
    ..0318) and ASR (P = 0.0067), INHBB was significant (P = 0.0360) for SCON trait. FSHB, FST, INHA, PRL, PRLR and LHB had no significant effects on any trait in this experiment. ..
  9. Miyoshi K, Shillingford J, Smith G, Grimm S, Wagner K, Oka T, et al. Signal transducer and activator of transcription (Stat) 5 controls the proliferation and differentiation of mammary alveolar epithelium. J Cell Biol. 2001;155:531-42 pubmed
    ..These data demonstrate that signaling via the PrlR and Stat5 is critical for the proliferation and differentiation of mammary alveoli during pregnancy. ..
  10. Bispham J, Gardner D, Gnanalingham M, Stephenson T, Symonds M, Budge H. Maternal nutritional programming of fetal adipose tissue development: differential effects on messenger ribonucleic acid abundance for uncoupling proteins and peroxisome proliferator-activated and prolactin receptors. Endocrinology. 2005;146:3943-9 pubmed
    ..In conclusion, we have shown, for the first time, differential effects of maternal nutrition on key regulatory components of fetal fat metabolism...
  11. Halperin J, Devi Y, Devi S, Elizur S, Stocco C, Shehu A, et al. Prolactin signaling through the short form of its receptor represses forkhead transcription factor FOXO3 and its target gene galt causing a severe ovarian defect. Mol Endocrinol. 2008;22:513-22 pubmed
    ..We also provide evidence of a link between the premature ovarian failure seen in mice expressing RS and in mice with FOXO3 gene deletion as well as in human with Galt mutation. ..
  12. Huang K, Ueda E, Chen Y, Walker A. Paradigm-shifters: phosphorylated prolactin and short prolactin receptors. J Mammary Gland Biol Neoplasia. 2008;13:69-79 pubmed publisher
  13. Utama F, Tran T, Ryder A, LeBaron M, Parlow A, Rui H. Insensitivity of human prolactin receptors to nonhuman prolactins: relevance for experimental modeling of prolactin receptor-expressing human cells. Endocrinology. 2009;150:1782-90 pubmed publisher
    ..The biology and drug responsiveness of existing human cell lines may therefore not be representative of clinical cancers that are sensitive to circulating PRL. ..
  14. Foitzik K, Krause K, Nixon A, Ford C, Ohnemus U, Pearson A, et al. Prolactin and its receptor are expressed in murine hair follicle epithelium, show hair cycle-dependent expression, and induce catagen. Am J Pathol. 2003;162:1611-21 pubmed
    ..These data support the intriguing concept that PRL is generated locally in the hair follicle epithelium and acts directly in an autocrine or paracrine manner to modulate the hair cycle. ..
  15. Viitala S, Szyda J, Blott S, Schulman N, Lidauer M, Mäki Tanila A, et al. The role of the bovine growth hormone receptor and prolactin receptor genes in milk, fat and protein production in Finnish Ayrshire dairy cattle. Genetics. 2006;173:2151-64 pubmed
    ..In particular, the GHR F279Y has the highest influence on protein percentage and fat percentage while PRLR S18N markedly influences protein and fat yield. Furthermore, an interaction between the two loci is suggested. ..
  16. Canbay E, Degerli N, Gulluoglu B, Kaya H, Sen M, Bardakci F. Could prolactin receptor gene polymorphism play a role in pathogenesis of breast carcinoma?. Curr Med Res Opin. 2004;20:533-40 pubmed
    ..Polymorphism of prolactin receptors might play a role in mammary carcinogenesis as a consequence of intracellular changes of PRLR signalling.
  17. Flint D, Binart N, Kopchick J, Kelly P. Effects of growth hormone and prolactin on adipose tissue development and function. Pituitary. 2003;6:97-102 pubmed
    ..However, recent studies suggest that this may be a physiological response in which adipose tissue sites containing lymphoid tissue (such as mesenteric) show preservation of adipose tissue perhaps to support augmented immune responses. ..
  18. Craven A, Ormandy C, Robertson F, Wilkins R, Kelly P, Nixon A, et al. Prolactin signaling influences the timing mechanism of the hair follicle: analysis of hair growth cycles in prolactin receptor knockout mice. Endocrinology. 2001;142:2533-9 pubmed
    ..The pituitary PRL regulation of hair follicle cycles observed in seasonally responsive mammals may be a result of pituitary PRL interacting with a local regulatory mechanism. ..
  19. Riedlinger G, Okagaki R, Wagner K, Rucker E, Oka T, Miyoshi K, et al. Bcl-x is not required for maintenance of follicles and corpus luteum in the postnatal mouse ovary. Biol Reprod. 2002;66:438-44 pubmed
    ..Whereas luteal cells underwent apoptosis in the absence of the PrlR, no changes were observed in the absence of Stat5 or Bcl-x. ..
  20. Goffin V, Binart N, Touraine P, Kelly P. Prolactin: the new biology of an old hormone. Annu Rev Physiol. 2002;64:47-67 pubmed
    ..This review is aimed at critically discussing how these recent findings have renewed the manner in which PRL should be considered as a multifunctional hormone. ..
  21. Devi Y, Shehu A, Stocco C, Halperin J, Le J, Seibold A, et al. Regulation of transcription factors and repression of Sp1 by prolactin signaling through the short isoform of its cognate receptor. Endocrinology. 2009;150:3327-35 pubmed publisher
    ..Our in vivo and in culture data demonstrate that the PRL-RS activates a signaling pathway distinct from that of the PRL-RL. ..
  22. Zenkova T, Kulikov A, Bogorad R, Rozenkrants A, Platonova L, Shono N, et al. Expression of prolactin receptors in human liver during cholestasis of different etiology and secondary liver cancer. Bull Exp Biol Med. 2003;135:566-9 pubmed
    ..immunoperoxidase assay and computer analysis of photographic images revealed more intensive expression of prolactin receptors in hepatocytes of women compared to men...
  23. Detti L, Saed G, Jiang Z, Kruger M, Diamond M. The effect of estradiol on the expression of estrogen, progesterone, androgen, and prolactin receptors in human peritoneal fibroblasts. J Assist Reprod Genet. 2008;25:245-50 pubmed publisher
    ..The inflammatory-like changes manifested by adhesion fibroblasts enhance the anabolic hormones receptor expression (ER-alpha, ER-beta, PRL, and A-R), when exposed to estradiol. ..
  24. Harris J, Stanford P, Oakes S, Ormandy C. Prolactin and the prolactin receptor: new targets of an old hormone. Ann Med. 2004;36:414-25 pubmed
    ..Further knockout models have provided insight into the importance of PRL signaling intermediates and the advent of transcript profiling has allowed the elucidation of a number of PRL target genes. ..
  25. Goldhar A, Vonderhaar B, Trott J, Hovey R. Prolactin-induced expression of vascular endothelial growth factor via Egr-1. Mol Cell Endocrinol. 2005;232:9-19 pubmed
    ..The induction of VEGF by PRL was PRL receptor-, Jak2- and MAP kinase kinase-dependent. Our results indicate that PRL induces VEGF expression through Egr-1, and implicates VEGF as an intermediary of PRL-regulated angiogenesis. ..
  26. Biener E, Martin C, Daniel N, Frank S, Centonze V, Herman B, et al. Ovine placental lactogen-induced heterodimerization of ovine growth hormone and prolactin receptors in living cells is demonstrated by fluorescence resonance energy transfer microscopy and leads to prolonged phosphorylation of signal transducer and a. Endocrinology. 2003;144:3532-40 pubmed
  27. Hu Z, Meng J, Dufau M. Isolation and characterization of two novel forms of the human prolactin receptor generated by alternative splicing of a newly identified exon 11. J Biol Chem. 2001;276:41086-94 pubmed
    ..These receptors may therefore play important roles in the diversified actions of prolactin in human tissues. ..
  28. Nixon A, Ford C, Wildermoth J, Craven A, Ashby M, Pearson A. Regulation of prolactin receptor expression in ovine skin in relation to circulating prolactin and wool follicle growth status. J Endocrinol. 2002;172:605-14 pubmed
    ..These cycle-related patterns of PRLR expression suggest dynamic regulation of PRLR by prolactin, thereby modulating hormonal responsiveness of seasonally growing hair follicles...
  29. Freemark M, Avril I, Fleenor D, Driscoll P, Petro A, Opara E, et al. Targeted deletion of the PRL receptor: effects on islet development, insulin production, and glucose tolerance. Endocrinology. 2002;143:1378-85 pubmed
    ..02) than those in wild-type mice. On the other hand, the glucose response to ip insulin was normal. Our observations establish a physiologic role for lactogens in islet development and function. ..
  30. Tonko Geymayer S, Goupille O, Tonko M, Soratroi C, Yoshimura A, Streuli C, et al. Regulation and function of the cytokine-inducible SH-2 domain proteins, CIS and SOCS3, in mammary epithelial cells. Mol Endocrinol. 2002;16:1680-95 pubmed
  31. Kedzia C, Lacroix L, Ameur N, Ragot T, Kelly P, Caillou B, et al. Medullary thyroid carcinoma arises in the absence of prolactin signaling. Cancer Res. 2005;65:8497-503 pubmed
    ..These observations suggest a possible link between the appearance of this carcinoma and the absence of prolactin signaling. ..
  32. Clevenger C, Furth P, Hankinson S, Schuler L. The role of prolactin in mammary carcinoma. Endocr Rev. 2003;24:1-27 pubmed
    ..These findings indicate that antagonists of PRL/PRL receptor interaction or PRL receptor-associated signal transduction may be of considerable utility in the treatment of human breast cancer. ..
  33. Liby K, Neltner B, Mohamet L, Menchen L, Ben Jonathan N. Prolactin overexpression by MDA-MB-435 human breast cancer cells accelerates tumor growth. Breast Cancer Res Treat. 2003;79:241-52 pubmed
    ..These data support a role for breast PRL as a growth/anti-apoptotic factor and suggest that it may serve as a novel therapeutic target for the treatment of breast cancer. ..
  34. Ruffion A, Al Sakkaf K, Brown B, Eaton C, Hamdy F, Dobson P. The survival effect of prolactin on PC3 prostate cancer cells. Eur Urol. 2003;43:301-8 pubmed
    ..Further investigations are underway to determine the survival effect of PRL on the other two prostate cancer cell line. ..
  35. Fresno Vara J, Caceres M, Silva A, Martin Perez J. Src family kinases are required for prolactin induction of cell proliferation. Mol Biol Cell. 2001;12:2171-83 pubmed
    ..Consistently, transient expression of SrcDM in W53 cells also blocked PRL activation of Akt. These results demonstrate that activation of SFKs is required for cell proliferation induced by PRL. ..
  36. McHale K, Tomaszewski J, Puthiyaveettil R, LiVolsi V, Clevenger C. Altered expression of prolactin receptor-associated signaling proteins in human breast carcinoma. Mod Pathol. 2008;21:565-71 pubmed publisher
    ..Since these species are known to regulate prolactin-mediated actions, these results suggest multiple targets for modulating prolactin receptor-mediated growth and differentiation in breast cancer. ..
  37. Viengchareun S, Bouzinba Segard H, Laigneau J, Zennaro M, Kelly P, Bado A, et al. Prolactin potentiates insulin-stimulated leptin expression and release from differentiated brown adipocytes. J Mol Endocrinol. 2004;33:679-91 pubmed
    ..This study provides the first evidence for a functional link between PRL and energy balance via a cross-talk between insulin and PRL signaling pathways in brown adipocytes. ..
  38. Trott J, Hovey R, Koduri S, Vonderhaar B. Alternative splicing to exon 11 of human prolactin receptor gene results in multiple isoforms including a secreted prolactin-binding protein. J Mol Endocrinol. 2003;30:31-47 pubmed
    ..Taken together, these data indicate the presence of multiple isoforms of the hPRLR that may function to modulate the endocrine and autocrine effects of PRL in normal human tissue and cancer. ..
  39. Ducret T, Boudina S, Sorin B, Vacher A, Gourdou I, Liguoro D, et al. Effects of prolactin on intracellular calcium concentration and cell proliferation in human glioma cells. Glia. 2002;38:200-14 pubmed
    ..Furthermore, PRL induced a dose-dependent increase in [3H]thymidine incorporation levels and in cellular growth and survival, detected by the MTT method. These data indicate that PRL induced mitogenesis of human glioma cells. ..
  40. Goffin V, Bernichtein S, Touraine P, Kelly P. Development and potential clinical uses of human prolactin receptor antagonists. Endocr Rev. 2005;26:400-22 pubmed
    ..We also speculate on the multiple questions that could be addressed with respect to the therapeutic use of PRL receptor antagonists in patients. ..
  41. Bogorad R, Ostroukhova T, Orlova A, Rubtsov P, Smirnova O. Prolactin receptors in rat cholangiocytes: regulation of level and isoform ratio is sex independent. Biochemistry (Mosc). 2006;71:178-84 pubmed
    ..Long isoform is predominant and induced primarily by cholestasis-induced factors. ..
  42. Bernichtein S, Kayser C, Dillner K, Moulin S, Kopchick J, Martial J, et al. Development of pure prolactin receptor antagonists. J Biol Chem. 2003;278:35988-99 pubmed
    ..These second generation human PRL antagonists are good candidates to be used as inhibitors of growth-promoting actions of PRL. ..
  43. Tomas A, Casellas J, Ramirez O, Munoz G, Noguera J, Sanchez A. High amino acid variation in the intracellular domain of the pig prolactin receptor (PRLR) and its relation to ovulation rate and piglet survival traits. J Anim Sci. 2006;84:1991-8 pubmed
  44. Mohammad Y, Perone M, Wang L, Ingleton P, Castro M, Lovejoy D. Expression of prolactin receptors and regulation of cell proliferation by prolactin, corticotropin-releasing factor, and corticosterone in a neuroblastoma cell line. Biochem Cell Biol. 2002;80:475-82 pubmed
    ..These data suggest that prolactin may act to increase the proliferation and regulation of neuroblastomas and that the effects of PRL may be modified by hypothalamo-pituitary-adrenal hormones. ..
  45. Ricken A, Traenkner A, Merkwitz C, Hummitzsch K, Grosche J, Spanel Borowski K. The short prolactin receptor predominates in endothelial cells of micro- and macrovascular origin. J Vasc Res. 2007;44:19-30 pubmed
    Controversial reports on prolactin receptors (PRL-R), the long and short form, on endothelial cells (EC) may be explained by the choice of EC derived from the micro- and macrovascular bed of either endocrine and non-endocrine organs...
  46. Grattan D, Pi X, Andrews Z, Augustine R, Kokay I, Summerfield M, et al. Prolactin receptors in the brain during pregnancy and lactation: implications for behavior. Horm Behav. 2001;40:115-24 pubmed
    ..We have observed marked changes in expression of prolactin receptors in specific hypothalamic nuclei during pregnancy and lactation...
  47. Asai Sato M, Nagashima Y, Miyagi E, Sato K, Ohta I, Vonderhaar B, et al. Prolactin inhibits apoptosis of ovarian carcinoma cells induced by serum starvation or cisplatin treatment. Int J Cancer. 2005;115:539-44 pubmed
    ..These findings indicate a responsiveness of ovarian carcinomas to prolactin and suggest that the prolactin/prolactin receptor system may be a new therapeutic target of ovarian carcinomas. ..
  48. Wagner K, Krempler A, Triplett A, Qi Y, George N, Zhu J, et al. Impaired alveologenesis and maintenance of secretory mammary epithelial cells in Jak2 conditional knockout mice. Mol Cell Biol. 2004;24:5510-20 pubmed
  49. Oakes S, Robertson F, Kench J, Gardiner Garden M, Wand M, Green J, et al. Loss of mammary epithelial prolactin receptor delays tumor formation by reducing cell proliferation in low-grade preinvasive lesions. Oncogene. 2007;26:543-53 pubmed
    ..this effect at an ill defined point in the carcinogenic process, via mechanisms involving direct action via prolactin receptors within mammary epithelium and/or indirect action through regulation of other hormones such as estrogen and ..
  50. Kmieć M, Terman A. Associations between the prolactin receptor gene polymorphism and reproductive traits of boars. J Appl Genet. 2006;47:139-41 pubmed
    ..45, AB at 0.35 and BB at 0.20. We found associations between PRLR genotype and ejaculate volume, sperm concentration, percentage of live sperm, and number of live sperm in the ejaculate (P < 0.01). ..
  51. Telleria C, Parmer T, Zhong L, Clarke D, Albarracin C, Duan W, et al. The different forms of the prolactin receptor in the rat corpus luteum: developmental expression and hormonal regulation in pregnancy. Endocrinology. 1997;138:4812-20 pubmed
  52. Jabbour H, Critchley H, Boddy S. Expression of functional prolactin receptors in nonpregnant human endometrium: janus kinase-2, signal transducer and activator of transcription-1 (STAT1), and STAT5 proteins are phosphorylated after stimulation with prolactin. J Clin Endocrinol Metab. 1998;83:2545-53 pubmed
    ..The target genes activated by PRL in the glandular epithelium of the nonpregnant human endometrium remain to be elucidated. ..
  53. Ormandy C, Hall R, Manning D, Robertson J, Blamey R, Kelly P, et al. Coexpression and cross-regulation of the prolactin receptor and sex steroid hormone receptors in breast cancer. J Clin Endocrinol Metab. 1997;82:3692-9 pubmed
    ..These results indicate that receptors for sex steroids and PRL are coexpressed and are cross-regulated, providing a potential mechanism for the observed synergy among estrogen, progesterone, and PRL in the control of tumor growth. ..