Characterization of brain neurons that express enzymes mediating neurosteroid biosynthesis
Roberto C. Agís-Balboa; Graziano Pinna; Adrian Zhubi; Ekrem Maloku; Marin Veldic; Erminio Costa; Alessandro Guidotti
Proceedings of the National Academy of Sciences2006
Summary (paraphrased)
Using in situ hybridization combined with neuronal and glial markers, the authors mapped 5α-reductase type I and 3α-hydroxysteroid dehydrogenase — the two enzymes that convert progesterone and deoxycorticosterone into allopregnanolone and THDOC — across mouse and rat brain. Both enzymes colocalize in glutamatergic principal neurons of cortex, hippocampus, and olfactory bulb, and in major GABAergic output neurons, but are absent from glia and cortical interneurons. The study proves the brain manufactures these neurosteroids locally via the type I isoenzyme, independent of peripheral glands.
Why it’s in the systems review
Powers' model and the Melcangi group's CSF findings both turn on where neurosteroids are made; this study proves the brain synthesizes allopregnanolone and THDOC locally via 5α-reductase type I, independent of gonads or adrenals. That means finasteride's CNS effects cannot be dismissed as secondary to peripheral DHT loss — and it explains how neurosteroid disruption could survive castration, a specific claim in Powers' theorizing. The type I anatomical map is the essential background for the isoenzyme division of labor shown in MECH-008.
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