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Review
. 2009 Aug;55(4):351-5.
doi: 10.1262/jrd.20249.

Roles of progranulin in sexual differentiation of the developing brain and adult neurogenesis

Masatoshi Suzuki  1 , Hwi-Cheul Lee, Yuko Kayasuga, Shuichi Chiba, Taku Nedachi, Takashi Matsuwaki, Keitaro Yamanouchi, Masugi Nishihara
Affiliations
Review

Roles of progranulin in sexual differentiation of the developing brain and adult neurogenesis

Masatoshi Suzuki et al. J Reprod Dev. 2009 Aug.

Abstract

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.

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Figures

Fig. 1
Fig. 1
Hypothesis of the roles of PGRN in the developing and adult brain. Estrogen converted from androgen by aromatase increases PGRN expression in neurons. The secreted PGRN or cleaved GRN peptides modulates the proliferation and differentiation of neurons and/or glial cells in an autocrine and/or paracrine manner, and consequently masculinizes the neuronal circuit in developing brain and modulates neurogenesis and neurodegeneration in adult and aged brain. Exposure to endocrine disruptors (EDCs) may lead inappropriate expression of PGRN gene. Astrocytes may influence protease activity by secretory leukocyte protease inhibitor (SLPI) and control the levels of PGRN and GRN peptides as in seen within wound healing in peripheral tissues.
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