Sex steroids synthesized in the hippocampus as novel neurotn phic factors acutely improving learning and memory efficacy

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In the present study, the synthesis of sex steroids, including dehydroepiandrosterone (DHEA), testosterone and 17β-estradiol, has been demonstrated in the adult rat hippocampus by metabolite analysis. The main path for the conversion from DHEA to testosterone in the hippocampus was shown to be 'DHEA→androstenediol→testosterone', which was different from the case in testis (DHEA→androstenedione→testosterone). With immunoelectron microscopy, the localization of essential enzymes for estrogen synthesis, cytochromes P45O17α and P450 aromatase, was demonstrated on membranous structures within spines of principal-neurons at hippocampal CA1 region. The localization of estrogen receptor a in the same structure was also demonstrated. Taken together, it seems to be plausible that estradiol plays a neuromodulative effect in the spine in which it was synthesized or in the spines located in adjacent places via membrane estrogen receptor α.Furthermore, 2-hour treatment of hippocampal slices with estradiol was observed to induce the growth of spine length and the increase of the spine density in CA1 region. Estradiol might exert its effect on neuronal signal transmission via this neurogrowth factor-like action.