Biosynthesis, mode of action, and functional significance of neurosteroids in the purkinje cell

Kazuyoshi Tsutsui, Kazuyoshi Ukena, Hirotaka Sakamoto, Shin Ichiro Okuyama, Shogo Haraguchi

    Research output: Contribution to journalArticle

    24 Citations (Scopus)

    Abstract

    The brain has traditionally been considered to be a target site of peripheral steroid hormones. In addition to this classical concept, we now know that the brain has the capacity to synthesize steroids de novo from cholesterol, the so-called "neurosteroids." In the middle 1990s, the Purkinje cell, an important cerebellar neuron, was identified as a major site for neurosteroid formation in the brain of mammals and other vertebrates. This discovery has provided the opportunity to understand neuronal neurosteroidogenesis in the brain. In addition, biological actions of neurosteroids are becoming clear by the studies using the Purkinje cell, an excellent cellular model, which is known to play an important role in memory and learning processes. Based on the studies on mammals over the past decade, it is considered that the Purkinje cell actively synthesizes progesterone and estradiol from cholesterol during neonatal life, when cerebellar neuronal circuit formation occurs. Both progesterone and estradiol promote dendritic growth, spinogenesis, and synaptogenesis via each cognate nuclear receptor in the developing Purkinje cell. Such neurosteroid actions mediated by neurotrophic factors may contribute to the formation of cerebellar neuronal circuit during neonatal life. 3α,5α-Tetrahydroprogesterone (allopregnanolone), a progesterone metabolite, is also synthesized in the cerebellum and considered to act as a survival factor of Purkinje cells in the neonate. This review summarizes the current knowledge regarding the biosynthesis, mode of action, and functional significance of neurosteroids in the Purkinje cell during development in terms of synaptic formation of cerebellar neuronal networks.

    Original languageEnglish
    Article numberArticle 61
    JournalFrontiers in Endocrinology
    Volume2
    Issue numberOCT
    DOIs
    Publication statusPublished - 2011

    Fingerprint

    Purkinje Cells
    Neurotransmitter Agents
    Progesterone
    Brain
    Mammals
    Estradiol
    Steroids
    Cholesterol
    Pregnanolone
    Nerve Growth Factors
    Cytoplasmic and Nuclear Receptors
    Cerebellum
    Vertebrates
    Learning
    Hormones
    Neurons
    Growth

    Keywords

    • Allopregnanolone
    • Dendritic growth
    • Estradiol
    • Neuronal circui
    • Neurosteroids
    • Progesterone
    • Purkinje cell
    • Synaptogenesis

    ASJC Scopus subject areas

    • Endocrinology, Diabetes and Metabolism

    Cite this

    Biosynthesis, mode of action, and functional significance of neurosteroids in the purkinje cell. / Tsutsui, Kazuyoshi; Ukena, Kazuyoshi; Sakamoto, Hirotaka; Okuyama, Shin Ichiro; Haraguchi, Shogo.

    In: Frontiers in Endocrinology, Vol. 2, No. OCT, Article 61, 2011.

    Research output: Contribution to journalArticle

    Tsutsui, Kazuyoshi ; Ukena, Kazuyoshi ; Sakamoto, Hirotaka ; Okuyama, Shin Ichiro ; Haraguchi, Shogo. / Biosynthesis, mode of action, and functional significance of neurosteroids in the purkinje cell. In: Frontiers in Endocrinology. 2011 ; Vol. 2, No. OCT.
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