Expression, localization and possible actions of 25-Dx, a membraneassociated putative progesterone-binding protein, in the developing Purkinje cell of the cerebellum: A new insight into the biosynthesis, metabolism and multiple actions of progesterone as a neurosteroid

Hirotaka Sakamoto, Kazuyoshi Ukena, Mitsuhiro Kawata, Kazuyoshi Tsutsui

Research output: Contribution to journalReview article

18 Citations (Scopus)

Abstract

Neurosteroids are now known to be steroids that are synthesized de novo from cholesterol in the central and peripheral nervous systems of vertebrates through mechanisms at least partly independent of peripheral steroidogenic glands, such as the adrenal and gonads. A series of our studies have demonstrated that the rat Purkinje cell, a cerebellar neuron, actively produces progesterone de novo from cholesterol only during neonatal life and progesterone promotes dendritic growth, spinogenesis and synaptogenesis via its nuclear receptor in this neuron. Thus the Purkinje cell serves as an excellent cellular model for understanding the formation of cerebellar neuronal circuit in relation to genomic neurosteroid actions. Recently, we have further found that Purkinje cells express the putative membrane progesterone receptor, 25-Dx in rats. By immunocytochemistry, the expression of 25-Dx was localized in the Purkinje cell and external granule cell layer. RT-PCR and Western immunoblot analyses revealed the expressions of 25-Dx and its mRNA in the rat cerebellum, which increased during neonatal life. Therefore, progesterone would promote dendritic growth, spinogenesis and synaptogenesis via 25-Dx as well as its nuclear receptor in the Purkinje cell in the neonate. Because the subcellular localization of 25-Dx was associated with membrane structures of the endoplasmic reticulum and Golgi, 25-Dx may also play a role in the regulation of neurosteroidogenesis in the developing Purkinje cell. Here we summarize the advances made in our understanding of the expression, localization and its possible actions of 25-Dx in the developing Purkinje cell.

Original languageEnglish
Pages (from-to)18-25
Number of pages8
JournalCerebellum
Volume7
Issue number1
DOIs
Publication statusPublished - Mar 1 2008
Externally publishedYes

Keywords

  • 25-Dx
  • Membrane progesterone receptor
  • Neurosteroids
  • Nongenomic action
  • Purkinje cell

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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