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Gene Review

PRL  -  prolactin

Bos taurus

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Disease relevance of PRL


High impact information on PRL

  • The site of methylation in the 3' end of prolactin mRNA was determined [6].
  • An in vitro methylation system was developed in which bovine prolactin mRNA, synthesized in vitro with T7 RNA polymerase, was accurately methylated in a HeLa cell nuclear extract [6].
  • Hormone-mediated repression: a negative glucocorticoid response element from the bovine prolactin gene [7].
  • In mammotrophs, heavy PRL labeling was observed over secretory granule matrices (including the immature matrices at the trans Golgi surface) and also over Golgi cisternae [8].
  • All somatotrophs and mammotrophs were heavily positive for GH and PRL, respectively, and were found to contain small amounts of the other hormone as well, which, however, was almost completely absent from granules, and was more concentrated in the Golgi complex, admixed with the predominant hormone [8].

Chemical compound and disease context of PRL


Biological context of PRL

  • These data support the concept that greater responsiveness and sensitivity to PRL during transition to lactation may be associated with an increase in subsequent milk yield [14].
  • Prior to PRL treatment, SDPP animals had greater lymphocyte proliferation and neutrophil chemotaxis relative to LDPP animals [15].
  • PRL mRNA expression was less in the regressed stage (days 19-21 after ovulation) than in the other stages [16].
  • Blocking experiments with anti-prolactin (PRL) antibody led to a 60% decrease in cell growth [17].
  • While PRL is known to activate Jak2-Stat5 (signal transducer and activator of transcription 5) signaling pathway, the mechanism by which cell proliferation is stimulated is less known [18].

Anatomical context of PRL

  • During the dry period, PRL and PRL-R mRNA were analyzed biweekly in plasma and lymphocytes, respectively [14].
  • These results demonstrate that the bovine mammary gland is responsive to exogenous PRL during early lactation [19].
  • Incorporation of [(3)H]thymidine into DNA was not affected by frequent milking or PRL treatment; however, analysis of autoradiograms revealed that stromal cell proliferation was greater in 4x cows [19].
  • Gram-negative bacterial lipopolysaccharide (LPS) and the Gram-positive bacterial lipoteichoic acid (LTA) substantially upregulated transcriptional expression driven by the Saa3 promoter in bovine mammary epithelial cells by 18.5-fold and 12.5-fold, respectively, whereas the lactogenic hormone, prolactin (PRL) stimulated a 3.5-fold increase [20].
  • We also measured the levels of PRL mRNA in cultured luteal cells and luteal endothelial cells [16].

Associations of PRL with chemical compounds

  • The minimal Saa3 promoter fragment that retained responsiveness to LPS, LTA, or PRL was 352 bp in size [20].
  • Concentrations of GH, PRL, estrogens (E(2)), progesterone (P(4)) and testosterone (T) were measured in follicular and cystic fluids [1].
  • Exposure of cultured luteal cells obtained from mid-stage CL (days 8-12) to bovine PRL (100, 200 ng/ml) for 24 hr did not affect P4 and PGF2alpha production by the cells [16].
  • Furthermore, the effect of PRL on progesterone (P4) and prostaglandin (PG) F2alpha production by cultured bovine luteal cells was examined [16].
  • Dex inhibition was reversed by the higher concentration of PRL added to cells [18].

Physical interactions of PRL


Enzymatic interactions of PRL

  • We have previously characterized the phosphorylation of bovine PRL and wish to determine whether a similar kinase activity phosphorylates bovine GH [24].

Regulatory relationships of PRL

  • These studies define the basis of cellular trafficking of PRLR isoforms and increase our understanding of control of target cell responsiveness by PRL [25].
  • The inhibitory effects of the trans-10, cis-12 CLA isomer on PRL-induced IDH1 expression accumulation were confirmed by quantitative real time PCR and western-blotting analysis [26].
  • Two-dimensional immunoblot analyses of colostrum and milk from healthy cows, as well as conditioned medium from PRL or LPS stimulated bovine mammary epithelial cells confirmed the differential production and secretion of M-SAA3 while other SAA isoforms were not detected [27].
  • Plasma concentrations of PRL increased (P less than .01) with age (r = +0.938) in control heifers while plasma TSH and GH were not significantly related to age [28].
  • We hypothesized that this effect is due to increased growth of mammary cells in response to enhanced prolactin signaling to influence the insulin-like growth factor (IGF) axis [29].

Other interactions of PRL


Analytical, diagnostic and therapeutic context of PRL

  • Semiquantitative RT-PCR analysis revealed that the mRNAs for PRL and its two receptors, l- and s-PRLR, were expressed in all luteal stages examined [16].
  • On tissues treated with 250 ng/mL of leptin, GH and PRL mRNA, as well as protein content, were estimated by reverse transcription-PCR and Western immunoblotting, respectively [32].
  • 16K PRL was generated by the proteolysis of rat 23K PRL with a particulate fraction from rat mammary gland homogenates and purified by gel filtration [30].
  • PRL in the serum was determined by radioimmunoassay (RIA) [33].
  • Using the membrane-bound receptor and bovine serum, the serum level of PRL was determined by radioreceptor assay (RRA) [33].


  1. Growth hormone but not prolactin concentrations in the fluid of bovine ovarian cysts are related to the cystic stage of luteinization. Borromeo, V., Bramani, S., Berrini, A., Sironi, G., Finazzi, M., Cremonesi, F., Secchi, C. Theriogenology (1996) [Pubmed]
  2. Bioactive recombinant methionyl bovine prolactin: structure-function studies using site-specific mutagenesis. Luck, D.N., Gout, P.W., Beer, C.T., Smith, M. Mol. Endocrinol. (1989) [Pubmed]
  3. Mechanism of thyroid hormone inhibition of thyrotropin-releasing hormone action. Hinkle, P.M., Perrone, M.H., Schonbrunn, A. Endocrinology (1981) [Pubmed]
  4. Purification and characterization of bovine placental lactogen. Murthy, G.S., Schellenberg, C., Friesen, H.G. Endocrinology (1982) [Pubmed]
  5. Effect of mammalian growth hormone and prolactin on the growth of hypophysectomized chickens. King, D.B., Scanes, C.G. Proc. Soc. Exp. Biol. Med. (1986) [Pubmed]
  6. An in vitro system for accurate methylation of internal adenosine residues in messenger RNA. Narayan, P., Rottman, F.M. Science (1988) [Pubmed]
  7. Hormone-mediated repression: a negative glucocorticoid response element from the bovine prolactin gene. Sakai, D.D., Helms, S., Carlstedt-Duke, J., Gustafsson, J.A., Rottman, F.M., Yamamoto, K.R. Genes Dev. (1988) [Pubmed]
  8. Sorting of three secretory proteins to distinct secretory granules in acidophilic cells of cow anterior pituitary. Hashimoto, S., Fumagalli, G., Zanini, A., Meldolesi, J. J. Cell Biol. (1987) [Pubmed]
  9. Variables associated with peripartum traits in dairy cows. VII. Hormones, calf traits and subsequent milk yield. Erb, R.E., Chew, B.P., Malven, P.V., D'Amico, M.F., Zamet, C.N., Colenbrander, V.F. J. Anim. Sci. (1980) [Pubmed]
  10. Bovine posterior pituitary extract stimulates prolactin release from the anterior pituitary gland in vitro and in vivo in cattle. Hashizume, T., Sasaki, T., Nonaka, S., Hayashi, T., Takisawa, M., Horiuchi, M., Hirata, T., Kasuya, E. Reprod. Domest. Anim. (2005) [Pubmed]
  11. Evidence for photosensitive regulation of prolactin secretion in prepubertal bulls. Petitclerc, D., Chapin, L.T., Harkins, P.A., Tucker, H.A. Proc. Soc. Exp. Biol. Med. (1983) [Pubmed]
  12. Interaction of endophyte-infected fescue and heat stress on ovarian function in the beef heifer. Burke, J.M., Spiers, D.E., Kojima, F.N., Perry, G.A., Salfen, B.E., Wood, S.L., Patterson, D.J., Smith, M.F., Lucy, M.C., Jackson, W.G., Piper, E.L. Biol. Reprod. (2001) [Pubmed]
  13. Hormonal modulation of phagocytosis and intracellular growth of Mycobacterium avium ss. paratuberculosis In bovine peripheral blood monocytes. Feola, R.P., Collins, M.T., Czuprynski, C.J. Microb. Pathog. (1999) [Pubmed]
  14. Effects of photoperiod during the dry period on prolactin, prolactin receptor, and milk production of dairy cows. Auchtung, T.L., Rius, A.G., Kendall, P.E., McFadden, T.B., Dahl, G.E. J. Dairy Sci. (2005) [Pubmed]
  15. Prolactin mediates photoperiodic immune enhancement: effects of administration of exogenous prolactin on circulating concentrations, receptor expression, and immune function in steers. Auchtung, T.L., Dahl, G.E. Biol. Reprod. (2004) [Pubmed]
  16. Bovine corpus luteum is an extrapituitary site of prolactin production. Shibaya, M., Murakami, S., Tatsukawa, Y., Skarzynski, D.J., Acosta, T.J., Okuda, K. Mol. Reprod. Dev. (2006) [Pubmed]
  17. The short prolactin receptor predominates in endothelial cells of micro- and macrovascular origin. Ricken, A.M., Traenkner, A., Merkwitz, C., Hummitzsch, K., Grosche, J., Spanel-Borowski, K. J. Vasc. Res. (2007) [Pubmed]
  18. Prolactin (PRL)-PRL receptor system increases cell proliferation involving JNK (c-Jun amino terminal kinase) and AP-1 activation: inhibition by glucocorticoids. Olazabal, I., Muñoz, J., Ogueta, S., Obregón, E., García-Ruiz, J.P. Mol. Endocrinol. (2000) [Pubmed]
  19. Mammary response to exogenous prolactin or frequent milking during early lactation in dairy cows. Wall, E.H., Crawford, H.M., Ellis, S.E., Dahl, G.E., McFadden, T.B. J. Dairy Sci. (2006) [Pubmed]
  20. Bovine serum amyloid A3 gene structure and promoter analysis: Induced transcriptional expression by bacterial components and the hormone prolactin. Larson, M.A., Weber, A., McDonald, T.L. Gene (2006) [Pubmed]
  21. Carboxypeptidase E, a peripheral membrane protein implicated in the targeting of hormones to secretory granules, co-aggregates with granule content proteins at acidic pH. Rindler, M.J. J. Biol. Chem. (1998) [Pubmed]
  22. In vivo effect of growth hormone on DNA synthesis and expression of milk protein genes in the rabbit mammary gland. Zebrowska, T., Siadkowska, E., Zwierzchowski, L., Gajewska, A., Kochman, K. J. Physiol. Pharmacol. (1997) [Pubmed]
  23. Lactogenic effect of bovine placental lactogen on pregnant rabbit but not pregnant heifer mammary gland explants. Byatt, J.C., Bremel, R.D. J. Dairy Sci. (1986) [Pubmed]
  24. GH kinase activity in bovine anterior pituitary subcellular fractions. Wicks, J.R., Brooks, C.L. Endocrine (1999) [Pubmed]
  25. Multiple internalization motifs differentially used by prolactin receptor isoforms mediate similar endocytic pathways. Lu, J.C., Scott, P., Strous, G.J., Schuler, L.A. Mol. Endocrinol. (2002) [Pubmed]
  26. Trans-10, Cis-12 Conjugated Linoleic Acid Inhibits Prolactin-Induced Cytosolic NADP+-Dependent Isocitrate Dehydrogenase Expression in Bovine Mammary Epithelial Cells. Liu, W., Degner, S.C., Romagnolo, D.F. J. Nutr. (2006) [Pubmed]
  27. Differential expression and secretion of bovine serum amyloid A3 (SAA3) by mammary epithelial cells stimulated with prolactin or lipopolysaccharide. Larson, M.A., Weber, A., Weber, A.T., McDonald, T.L. Vet. Immunol. Immunopathol. (2005) [Pubmed]
  28. Growth rate and secretion of pituitary hormones in relation to age and chronic treatment with thyrotropin-releasing hormone in prepubertal dairy heifers. Davis, S.L., Sasser, R.G., Thacker, D.L., Ross, R.H. Endocrinology (1977) [Pubmed]
  29. Exposure to short day photoperiod during the dry period enhances mammary growth in dairy cows. Wall, E.H., Auchtung, T.L., Dahl, G.E., Ellis, S.E., McFadden, T.B. J. Dairy Sci. (2005) [Pubmed]
  30. A specific, high affinity, saturable binding site for the 16-kilodalton fragment of prolactin on capillary endothelial cells. Clapp, C., Weiner, R.I. Endocrinology (1992) [Pubmed]
  31. Cloning of bovine prolactin cDNA and evolutionary implications of its sequence. Miller, W.L., Coit, D., Baxter, J.D., Martial, J.A. DNA (1981) [Pubmed]
  32. Role of leptin on growth hormone and prolactin secretion by bovine pituitary explants. Accorsi, P.A., Munno, A., Gamberoni, M., Viggiani, R., De Ambrogi, M., Tamanini, C., Seren, E. J. Dairy Sci. (2007) [Pubmed]
  33. Radioreceptor assay of serum prolactin using nitrocellulose membrane-immobilized mammary prolactin receptor. Suzuki, M., Kohmoto, K., Sakai, S. Anal. Biochem. (1992) [Pubmed]
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