Skip to main content
Log in

Expression and function of leptin and its receptor in mouse mammary gland

  • Published:
Science in China Series C: Life Sciences Aims and scope Submit manuscript

Abstract

Leptin is an autocrine and paracrine factor which affects the development of duct, formation of gland alveolus, expression of milk protein gene and onset involution of mammary gland. In order to know the function and mechanism of leptin in mammary gland, the protein expression and localization of leptin and its long form receptor (OB-Rb) were detected by a confocal laser scanning microscope. To study the impacts of leptin on mammary gland and leptin signal transduction pathway in pregnancy-, lactation-and involution-stage mammary gland, explants were cultured and Western blotting was used. The results showed that in the whole development cycle of mammary gland, the expression of leptin and OB-Rb was in positive correlation. In virgin the leptin expression was the highest and then decreased in pregnancy. In lactation the expression of leptin was low and upgraded in involution, and recovered to the original level about virgin on involution 13 d. The localization of leptin and OB-Rb revealed that leptin induced the expression of OB-Rb specifically and controlled the development and physiological function of the mammary gland by binding to OB-Rb. In pregnancy stage, leptin stimulated proliferation and differentiation of ductal epithelial cells by JAK-MAPK signal pathway. In lactation, leptin induced gene expression of β-casein by JAK-STAT5 signal pathway, and in involution leptin induced mammary epithelial cell apoptosis and mammary gland restitution by JAK-STAT3 signal pathway.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Zhang Y, Proenca R, Maffei M, et al. Positional cloning of the mouse obese gene and its human homologue. Nature, 1994, 372: 425–432

    Article  PubMed  CAS  Google Scholar 

  2. Houseknecht K L, Baile C A, Matteri R L, et al. The biology of leptin: A review. J Anim Sci, 1998, 76: 1405–1420

    PubMed  CAS  Google Scholar 

  3. Wauters M, Considine R V, van Gaal L F. Human leptin: From an adipocyte hormone to an endocrine mediator. Eur J Endocrinol, 2000, 143: 293–311

    Article  PubMed  CAS  Google Scholar 

  4. Hu X, Juneja S C, Maihle N J, et al. Leptin—A growth factor in normal and malignant breast cells and for normal mammary gland development. J Natl Cancer Inst, 2002, 94: 1704–1711

    PubMed  CAS  Google Scholar 

  5. Aoki N, Kawamura M, Matsuda T. Lactation-dependent down regulation of leptin production in mouse mammary gland. Biochim Biophys Acta, 1999, 1427: 298–306

    PubMed  CAS  Google Scholar 

  6. Baratta M, Grolli S, Tamanini C. Effect of leptin in proliferating and differentiated HC11 mouse mammary cells. Regul Pept, 2003, 113(1-3): 101–107

    Article  PubMed  CAS  Google Scholar 

  7. Bonnet M, Gourdou I, Leroux C, et al. Leptin expression in the ovine mammary gland: Putative sequential involvement of adipose, epithelial, and myoepithelial cells during pregnancy and lactation. J Anim Sci, 2002, 80: 723–728

    PubMed  CAS  Google Scholar 

  8. Elias J J, Pitelka D R, Armstrong R C. Changes in fat cell morphology during lactation in the mouse. Anat Rec, 1973, 177: 533–547

    Article  PubMed  CAS  Google Scholar 

  9. Feuermann Y, Mabjeesh S J, Shamay A. Leptin affects prolactin action on milk protein and fat synthesis in the bovine mammary gland. J Dairy Sci, 2004, 87(9): 2941–2946

    Article  PubMed  CAS  Google Scholar 

  10. Tartaglia L A, Dembski M, Weng X, et al. Identification and expression cloning of a leptin receptor OB-R. Cell, 1995, 83(7): 1263–1271

    Article  PubMed  CAS  Google Scholar 

  11. Baumann H, Morella K K, White D W, et al. The full-length leptin receptor has signaling capabilities of interleukin 6-type cytokine receptors. Proc Natl Acad Sci USA, 1996, 93(16): 8374–8378

    Article  PubMed  CAS  Google Scholar 

  12. Tartaglia L A. The leptin receptor. J Biol Chem, 1997, 272: 6093–6096

    PubMed  CAS  Google Scholar 

  13. Laud K, Gourdon I, Belair L, et al. Detection and regulation of leptin receptor mRNA in ovine mammary epithelial cells during pregnancy and lactation. FEBS Lett, 1999, 463: 194–198

    Article  PubMed  CAS  Google Scholar 

  14. Fantuzzi G, Faggioni R. Leptin in the regulation of immunity, inflammation and hematopoiesis. J Leukoc Biol, 2000, 68: 437–446

    PubMed  CAS  Google Scholar 

  15. Bjorbaek C, Uotani S, da Silva B, et al. Divergent signaling capacities of the long and short isoforms of the leptin receptor. J Biol Chem, 1997, 272(51): 32686–32695

    Article  PubMed  CAS  Google Scholar 

  16. Carpenter L R, Farruggella T J, Symes A, et al. Enhancing leptin response by preventing SH2-containing phosphatase 2 interaction with Ob receptor. Proc Natl Acad Sci USA, 1998, 95(11): 6061–6066

    Article  PubMed  CAS  Google Scholar 

  17. Banks A S, Davis S M, Bates S H, et al. Activation of downstream signals by the long form of the leptin receptor. J Biol Chem, 2000, 275(19): 14563–14572

    Article  PubMed  CAS  Google Scholar 

  18. Takahashi Y, Okimura Y, Mizuno I, et al. Leptin induces mitogen-activated protein kinase-dependent proliferation of C3H10T1/2 cells. J Biol Chem, 1997, 272: 12897–12900

    Article  PubMed  CAS  Google Scholar 

  19. Li C, Friedman J M. Leptin receptor activation of SH2 domain containing protein tyrosine phosphatase 2 modulates Ob receptor signal transduction. Proc Natl Acad Sci USA,1999, 96: 9677–9682

    Article  PubMed  CAS  Google Scholar 

  20. Bjorbaek C, El-Haschimi K, Frantz J D, et al. The role of SOCS-3 in leptin signaling and leptin resistance. J Biol Chem, 1999, 274: 30059–30065

    Article  PubMed  CAS  Google Scholar 

  21. Miyoshi K, Shillingford J M, Smith G H, et al. Signal transducer and activator of transcription (Stat) 5 controls the proliferation and differentiation of mammary alveolar epithelium. J Cell Biol, 2001, 155: 531–542

    Article  PubMed  CAS  Google Scholar 

  22. Liu X, Robinson G W, Wagner K U, et al. Stat5a is mandatory for adult mammary gland development and lactogenesis. Genes Dev, 1997, 11: 179–186

    Article  PubMed  CAS  Google Scholar 

  23. Teglund S, McKay C, Schuetz E, et al. Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses. Cell, 1998, 93: 841–850

    Article  PubMed  CAS  Google Scholar 

  24. Chehab F F, Lim M E, Lu R. Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nat Genet, 1996, 12: 318–320

    Article  PubMed  CAS  Google Scholar 

  25. Bjorbæk C, Lavery H J, Bates S H, et al. SOCS3 mediates feedback inhibition of the leptin receptor via Tyr985. J Biol Chem, 2000, 275: 40649–40657

    Article  Google Scholar 

  26. Hutt J A, O’Rourke J P, DeWille J. Signal transducer and activator of transcription 3 activates CCAAT enhancer-binding protein δ gene transcription in G0 growth-arrested mouse mammary epithelial cells and in involuting mouse mammary gland. J Biol Chem, 2000, 275: 29123–29131

    Article  PubMed  CAS  Google Scholar 

  27. Humphrey R C, Bierie B, Zhao L, et al. Deletion of Stat3 blocks mammary gland involution and extends functional competence of the secretory epithelium in the absence of lactogenic stimuli. Endocrinology, 2002, 143(9): 3641–3650

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Li QingZhang.

Additional information

Supported by the National Natural Science Foundation of China (Grant No. 30671538)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lin, Y., Li, Q. Expression and function of leptin and its receptor in mouse mammary gland. SCI CHINA SER C 50, 669–675 (2007). https://doi.org/10.1007/s11427-007-0077-2

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11427-007-0077-2

Keywords

Navigation