嗅球におけるステロイド合成酵素の局在

Neurosteroids are synthesized through mechanism at least partly independent of the peripheral steroidogenic glands, and their neurobiological actions seem to depend on the specific functions of various brain regions. However, little is known about neurosteroids function corresponding to specific structure and functions of the brain regions. Thus the present study analyzed localization of steroid-synthesizing enzymes in the rat and mouse olfactory bulb. RT-PCR and Western-blotting indicated the possible presence of almost all enzymes of steroid synthesis from cholesterol to estradiol, that is, cholesterol side chain cleavage enzyme (P450scc : cholesterol→pregnenolone), 3β-hydroxysteroid dehydrogenase/Δ5 - 4 isomerase (3β-HSD : pregnenolone→progesterone), 17α-hydroxylase/C17-C20lyase (P450c17 : progesterone→ androstenedione), 17β-hydroxysteroid dehydrogenase (17β-HSD : androstenedione→testosterone), 5α-reductase (5αR:testosterone→5α-dihydrotestosterone), and aromatase (testosterone→ estradiol). Immunohistochemistry confirmed that the 5α-reductase was mainly in glial cells with various immunoreactivity and co-localization pattern, but other enzymes were in bulbar neurons, and at least co-localized in mitral/tufted cells. In addition, so far analyzed, enzymatic activities of P450c17 (a key enzyme in sex steroid synthesis) and 17β-HSD were detected biochemically. These enzyme expression and activities were influenced under exposure of 17β-estradiol with various degrees. These findings indicated the presence of steroid-synthesizing activities, and thus of possible neurosteroid metabolism in the olfactory bulb.