Roles of Progranulin in Sexual Differentiation of the Developing Brain and Adult Neurogenesis

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  • SUZUKI Masatoshi
    The Waisman Center, The Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison
  • LEE Hwi-Cheul
    Department of Veterinary Physiology, Veterinary Medical Science, The University of Tokyo Animal Biotechnology Division, National Institute of Animal Science, RDA
  • KAYASUGA Yuko
    Department of Veterinary Physiology, Veterinary Medical Science, The University of Tokyo
  • CHIBA Shuichi
    Department of Veterinary Physiology, Veterinary Medical Science, The University of Tokyo
  • NEDACHI Taku
    Department of Veterinary Physiology, Veterinary Medical Science, The University of Tokyo
  • MATSUWAKI Takashi
    Department of Veterinary Physiology, Veterinary Medical Science, The University of Tokyo
  • YAMANOUCHI Keitaro
    Department of Veterinary Physiology, Veterinary Medical Science, The University of Tokyo
  • NISHIHARA Masugi
    Department of Veterinary Physiology, Veterinary Medical Science, The University of Tokyo

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Progranulin (PGRN) is a growth modulating factor released by a variety of cells. This molecule has gained the attention of the neuroscience community with recent discoveries of multifunctional roles of PGRN in normal brain and neurodegenerative disorders. We focus on novel roles of PGRN as a sex steroid-responsible gene in the developing and adult rodent brain. While the developing brain is feminine by default, hormone exposure, including androgen and estrogen, induces masculinization during the critical period. We have shown that PGRN is a sex steroid-responsible gene that may be involved in masculinization of the perinatal rat brain. We also found that in adult rats PGRN gene expression was up-regulated by estrogen in the hippocampus, suggesting that PGRN may mediate the mitogenic effects of estrogen in the active area of neurogenesis. Since it has been recently reported that mutations in PGRN gene are responsible for a type of frontotemporal lobar degeneration in humans, PGRN appears to be also involved in modulating neurodegeneration. Together, PGRN gene expression is induced by estrogen in both developing and adult brains, and it may play multifunctional roles in the organization of functional masculinization in the developing brain and the maintenance of adult brain function.<br>

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