, Volume 43, Issue 2, pp 387–393 | Cite as

Pregnancy-associated plasma protein (PAPP)-A expressed in the mammary gland controls epithelial cell proliferation and differentiation

  • Makoto Nakasato
  • Hitoshi Kohsaka
  • Tetsuya Mizutani
  • Gen Watanabe
  • Kazuyoshi Taya
  • Kentaro Nagaoka
Original Article


Lactation is an important event in all-mammalian species. To investigate the role of pregnancy-associated plasma protein (PAPP)-A in lactogenesis, we determined (i) PAPP-A expression in mouse mammary glands and (ii) the biological functions of PAPP-A in mammary epithelial cells. PAPP-A mRNA level was low during early mid pregnancy and increased during mid-late pregnancy, and then slightly decreased during lactation. Cell proliferation signals, but not differentiation, increased PAPP-A mRNA expression in HC11 mammary epithelial cells. Treatment of recombinant PAPP-A protein stimulated HC11 cell proliferation and suppressed the expression of β-casein mRNA, which is one of the milk proteins and cell differentiation marker. Surprisingly, in forcing expression experiment, PAPP-A increased β-casein mRNA expression. Our data suggest that PAPP-A has different roles on intracellular expressing and extracellular treatment to mammary epithelial cells. Taken together, in early pregnancy, circulating PAPP-A protein might be supplied from other organs and stimulates mammary gland growth. In contrast, during mid-late pregnancy, local PAPP-A expression begins and enhances cell differentiation within mammary epithelial cell.


PAPP-A IGF Mammary gland Mammary epithelial cell 



The authors would like to thank Prof. Nobuyuki Miyasaka and Dr. Yoshinori Nonomura for valuable suggestions and comments.


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Makoto Nakasato
    • 1
  • Hitoshi Kohsaka
    • 1
  • Tetsuya Mizutani
    • 2
  • Gen Watanabe
    • 3
  • Kazuyoshi Taya
    • 3
  • Kentaro Nagaoka
    • 3
  1. 1.Department of Medicine and Rheumatology, and Global Center of Excellence Program, International Research Center for Molecular Science in Tooth and Bone Disease, Graduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityTokyoJapan
  2. 2.Research and Education Center for Prevention of Global Infectious Diseases of Animals, Faculty of AgricultureTokyo University of Agriculture and TechnologyTokyoJapan
  3. 3.Laboratory of Veterinary Physiology, Department of Veterinary Medicine, Faculty of AgricultureTokyo University of Agriculture and TechnologyFuchu, TokyoJapan

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