Skip to main content
SpringerLink
Log in

Nuclear Localisation of the Transcription Factor Stat5b is Associated with Ovine Milk Protein Gene Expression During Lactation but not During Late Pregnancy or Forced Weaning

  • Published:
The Histochemical Journal Aims and scope Submit manuscript

Abstract

Localisation patterns of the transcription factor Stat5b in the udders from pregnant, lactating and involuting ewes were compared with the expression patterns of two major milk protein genes α-lactalbumin and αS1 casein. Stat5b was detected in the cytoplasm and nuclei of epithelial cells at all stages of mammary gland development. A consistent positive relationship between the nuclear localisation of Stat5b in lactating mammary alveolar epithelial cells, and the presence of milk protein gene mRNA was apparent during lactation and early involution. Conversely, there was little evidence of nuclear localisation of Stat5b in non-lactating mammary alveolar epithelial cells during lactation and early involution. This supports the observation that during lactation, Stat5b may play a role in milk protein gene expression. However, during pregnancy and later involution, while Stat5b was observed to be present in mammary epithelial cell nuclei and cytoplasm, no relationship between this and the presence of milk protein gene mRNA was apparent. This suggests that during late pregnancy and in later involution, Stat5b may be involved in processes other than initiation of milk protein gene transcription.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References cited

  • Ali S (1998) Prolactin receptor regulates Stat5 tyrosine phosphorylation and nuclear translocation by two separate pathways. J Biol Chem 273: 7709–7716.

    Google Scholar 

  • Cella N, Groner B, Hynes NE (1998) Characterisation of Stat5a and Stat5b homodimers and heterodimers and their association with the glucocorticoid receptor in mammary cells. Mol Cell Biol 18: 1783–1792.

    Google Scholar 

  • Daly SE, Hartmann PE (1995a) Infant demand and milk supply. Part 1: Infant demand and milk production in lactating women. J Hum Lact 11: 21–26.

    Google Scholar 

  • Daly SE, Hartmann PE (1995b) Infant demand and milk supply. Part 2: The short-term control of milk synthesis in lactating women. J Hum Lact 11: 27–37.

    Google Scholar 

  • Demmer J, Burdon TG, Djiane J, Watson CJ, Clark AJ (1995) The proximal milk protein binding factor binding site is required for the prolactin responsiveness of the sheep beta-lactoglobulin promoter in Chinese hamster ovary cells. Mol Cell Endocrinol 107: 113–121.

    Google Scholar 

  • Forsyth I, Hayden TJ (1997) In: Peaker M, ed. Comparative Aspects of Lactation. London: Academic Press, pp. 135–163.

    Google Scholar 

  • Fritsche M, Mundt M, Merkle C, Jahne R, Groner B (1998) p53 suppresses cytokine induced, Stat5 mediated activation of transcription. Mol Cell Endocrinol 143: 143–154.

    Google Scholar 

  • Geenty KG (1979) Effects of weaning age on export lamb production. Proc NZ Soc An Prod 39: 202–210.

    Google Scholar 

  • Gordon K, Philp J, Burdon T, Binas B, Watson C (1997) In: Wild C, Peaker M, Taylor E, eds. Biological Signalling in the Mammary Gland. Hannah Research Institute, Ayr, pp. 172–173.

    Google Scholar 

  • Gouilleux F, Wakao H, Mundt M, Groner B (1994) Prolactin induces phosphorylation of Tyr694 of Stat5 (MGF), a prerequisite for DNA binding and induction of transcription. EMBO J 13: 4361–4369.

    Google Scholar 

  • Humphreys R, Hennighausen L (1999) Signal transducer and activator of transcription 5a influences mammary epithelial cell survival and tumorigenesis. Cell Growth & Diff 10(10): 685–694.

    Google Scholar 

  • Jahn GA, Daniel N, Jolivet G, Belair L, Bolefeysot C, Kelly PA, Djiane J (1997) In vivo study of prolactin (Prl) intracellular signalling during lactogenesis in the rat-Jak/Stat pathway is activated by Prl in the mammary gland but not in the liver. Bio Reprod 57: 894–900.

    Google Scholar 

  • Johnson HM, Torres BA, Green MM, Szente BE, Siler KI, Larkin 3rd J, Subramaniam PS (1998) Hypothesis: Ligand/receptor-assisted nuclear translocation of STATs. Proc Soc Exp Biol Med 218: 149–155.

    Google Scholar 

  • Kazansky A, Raught B, Lindsey S, Wang Y, Rosen J (1995) Regulation of mammary gland factor/Stat5a during mammary gland development. Mol Endocrinol 9: 1598–1609.

    Google Scholar 

  • Kuhn NJ (1997) In: Peaker M, ed. Comparative Aspects of Lactation. London: Academic Press, pp. 165–192.

    Google Scholar 

  • Li S, Rosen JM (1995) Nuclear factor I and mammary gland factor (STAT5) play a critical role in regulating rat whey acidic protein gene expression in transgenic mice. Mol Cell Biol 15: 2063–2070.

    Google Scholar 

  • Liu X, Robinson GW, Gouilleux F, Groner B, Hennighausen L (1995) Cloning and expression of Stat5 and an additional homologue (Stat5b) involved in prolactin signal transduction in mouse mammary tissue. Proc Natl Acad Sci USA 92: 8831–8835.

    Google Scholar 

  • Liu XW, Robinson GW, Hennighausen L (1996) Activation of Stat5a and Stat5b by tyrosine phosphorylation is tightly linked to mammary gland differentiation. Mol Endocrinol 10: 1496–1506.

    Google Scholar 

  • Liu X, Robinson GW, Wagner KU, Garrett L, Wynshaw-Boris A, Hennighausen L (1997) Stat5a is mandatory for adult mammary gland development and lactogenesis. Genes Dev 11: 179–186.

    Google Scholar 

  • McCracken JY, Molenaar AJ, Snell RJ, Davey HW, Wilkins RJ (1997) A polymorphic TG repeat present within the bovine STAT5A gene. Anim Genet 28: 459.

    Google Scholar 

  • McCracken JY, Molenaar AJ, Wilkins RJ, Grigor MR (1994) Spatial and temporal expression of the transferrin gene in the rat mammary gland. J Dairy Sci 77: 1828–1834.

    Google Scholar 

  • Molenaar AJ, Davis SR, Jack LJW, Wilkins RJ (1995) Expression of the butyrophilin gene, a milk fat globule membrane protein, is associated with the expression of the alphaS1casein gene. Histochem J 27: 388–394.

    Google Scholar 

  • Molenaar AJ, Davis SR, Wilkins RJ (1992) Expression of alphalactalbumin, alphaS1casein, and lactoferrin genes is heterogeneous in sheep and cattle mammary tissue. J Histochem Cytochem 40: 611–618.

    Google Scholar 

  • Molenaar AJ, Kuys YM, Davis SR, Wilkins RJ, Mead PE, Tweedie JW (1996a) Elevation of lactoferrin gene expression in developing, ductal, resting, and regressing parenchymal epithelium of the ruminant mammary gland. J Dairy Sci 79: 1198–1208.

    Google Scholar 

  • Molenaar AJ, Wilkins RJ, Davis SR (1996b) Measurement of cell death by in situ end labelling of ruminant mammary gland tissue. Proc NZ Soc An Prod 56: 71–76.

    Google Scholar 

  • Mui AL, Wakao H, Kinoshita T, Kitamura T, Miyajima A(1996) Suppression of interleukin-3-induced gene expression by a C-terminal truncated Stat5: Role of Stat5 in proliferation. EMBO J 15: 2425–2433.

    Google Scholar 

  • Philp JA, Burdon TG, Watson CJ (1996) Differential activation of STATs 3 and 5 during mammary gland development. FEBS Lett 396: 77–80.

    Google Scholar 

  • Raught B, Liao WS, Rosen JM (1995) Developmentally and hormonally regulated CCAAT/enhancer-binding protein isoforms influence betacasein gene expression. Mol Endocrinol 9: 1223–1232.

    Google Scholar 

  • Rentrop M, Knapp B, Winter H, Schweizer J (1986) Aminoalkylsilane-treated glass slides as support for in situ hybridization of keratincDNAs to frozen tissue sections under varying fixation and pretreatment conditions. Histochem J 18: 271–276.

    Google Scholar 

  • Rosen JM, Rogers JR, Couch CH, Bisbee CA, David-Inouye Y, Campbell SM, Yu-Lee L-Y (1986) In: Hanson R, Goodridge A, eds. Metabolic Regulation: Application of Recombinant DNA Techniques. Vol. 478, New York: Annals of the New York Academy of Sciences, pp. 63–76.

    Google Scholar 

  • Schmitt-Ney M, Doppler W, Ball RK, Groner B (1991) β-Casein gene promoter activity is regulated by the hormone-mediated relief of transcriptional repression and a mammary-gland specific nuclear factor. Mol Cell Biol 11: 3745–3755.

    Google Scholar 

  • Schmitt-Ney M, Hofer P, Hynes NE, Groner B (1992) Mammary glandspecific nuclear factor activity is positively regulated by lactogenic hormones and negatively by milk stasis. Mol Endocrinol 6: 1988–1997.

    Google Scholar 

  • Teglund S, McKay C, Schuetz E, Van Deursen JM, Stravopodis D, Wang D, Brown M, Bodner S, Grosveld G, Ihle JN (1998) Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses. Cell 93: 841–850.

    Google Scholar 

  • Udy GB, Towers RP, Snell RG, Wilkins RJ, Park SH, Ram PA, Waxman DJ, Davey HW (1997) Requirement of Stat5b for sexual dimorphism of body growth rates and liver gene expression. Proc Natl Acad Sci USA 94: 7239–7244.

    Google Scholar 

  • Wakao H, Gouilleux F, Groner B (1994) Mammary gland factor (MGF) is a novel member of the cytokine regulated transcription factor gene family and confers the prolactin response. EMBO J 13: 2182–2191.

    Google Scholar 

  • Wakao H, Schmitt-Ney M, Groner B (1992) Mammary gland-specific nuclear factor is present in lactating rodent and bovine mammary tissue and composed of a single polypeptide of 89 kDA. J Biol Chem 267: 16365–16370.

    Google Scholar 

  • Wartmann M, Cella N, Hofer P, Groner B, Liu X, Hennighausen L, Hynes NE (1996) Lactogenic hormone activation of Stat5 and transcription of the beta-casein gene in mammary epithelial cells is independent of p42 ERK2 mitogen-activated protein kinase activity. J Biol Chem 271: 31863–31868.

    Google Scholar 

  • Watson CJ, Burdon TG (1996) Prolactin signal transduction mechanisms in the mammary gland: The role of the Jak/Stat pathway. Rev Reprod 1: 1–5.

    Google Scholar 

  • Wheeler TT, Kuys YM, Broadhurst MM, Molenaar AJ (1997) Mammary Stat5 abundance and activity are not altered with lactation state in cows. Mol Cell Endocrinol 133: 141–149.

    Google Scholar 

  • Wilkinson D (Ed.) (1992) In Situ Hybridization, A Practical Approach. Oxford: Oxford University Press, 34 pp.

    Google Scholar 

  • Yamashita H, Xu J, Erwin RA, Farrar WL, Kirken RA, Rui H (1998) Differential control of the phosphorylation state of proline-juxtaposed serine residues Ser725 of Stat5a and Ser730 of Stat5b in prolactin-sensitive cells. J Biol Chem 273: 30218–30224.

    Google Scholar 

  • Zamorano J, Wang HY, Wang R, Shi Y, Longmore GD, Keegan AD (1998) Regulation of cell growth by IL-2: role of STAT5 in protection from apoptosis but not in cell cycle progression. J Immunol 160: 3502–3512.

    Google Scholar 

  • Zinn SA, Broavo-Ureta B (1996) In: Philips CJC, ed. Progress in Dairy Health. Oxon: CAB International, pp. 59–85.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Food Science Platform, AgResearch, Ruakura Research Centre, Private Bag 3123, Hamilton, New Zealand

    Adrian J. Molenaar, Thomas T. Wheeler & Murray R. Grigor

Authors
  1. Adrian J. Molenaar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas T. Wheeler
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Murray R. Grigor
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Molenaar, A.J., Wheeler, T.T. & Grigor, M.R. Nuclear Localisation of the Transcription Factor Stat5b is Associated with Ovine Milk Protein Gene Expression During Lactation but not During Late Pregnancy or Forced Weaning. Histochem J 32, 265–274 (2000). https://doi.org/10.1023/A:1004002611259

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1004002611259

Keywords

Search

Navigation