抄録
The brain has traditionally been considered to be a target site of peripheral steroid hormones. By contrast, new findings over the past decade have shown that the brain itself also has the capability of forming steroids de novo from cholesterol, the so-called "neurosteroids". De novo neurosteroidogenesis in the brain is a conserved property of vertebrates. Recently the Purkinje cell, a cerebellar neuron, has been identified as a major site for neurosteroid formation in a variety of vertebrates. This is the first demonstration of de novo neuronal neurosteroidogenesis in the brain. Since this discovery, diverse actions of neurosteroids are becoming clear by the studies on mammals using the Purkinje cell as an excellent cellular model. In mammals, the Purkinje cell possesses several kinds of steroidogenic enzymes, such as cytochrome P450 side-chain cleavage enzyme (P450scc), 3β-hydroxysteroid dehydrogenase/Δ5-Δ4-isomerase (3β-HSD) etc., and actively synthesizes progesterone and 3α,5α-tetrahydroprogesterone (3α,5α-THP; allopregnanolone) de novo from cholesterol during neonatal life, when cerebellar cortical formation occurs. The Purkinje cell also expresses the key enzyme of estrogen formation, cytochrome P450 aromatase (P450arom), and may actively produce estradiol in the neonate. Both progesterone and estradiol promote dendritic growth, spinogenesis and synaptogenesis via each cognate nuclear receptor in Purkinje cells. 3α,5α-THP is also involved in Purkinje and granule cell survival. [J Physiol Sci. 2007;57 Suppl:S44]
