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Endocrinology, doi:10.1210/en.2009-0305
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Endocrinology Vol. 150, No. 11 5106-5112
Copyright © 2009 by The Endocrine Society

Comparison between Hippocampus-Synthesized and Circulation-Derived Sex Steroids in the Hippocampus

Yasushi Hojo1, Shimpei Higo1, Hirotaka Ishii, Yuuki Ooishi, Hideo Mukai, Gen Murakami, Toshihiro Kominami, Tetsuya Kimoto, Seijiro Honma, Donald Poirier and Suguru Kawato

Department of Biophysics and Life Sciences (S.H., Y.H., H.I., O.Y., H.M., G.M., T.K., S.K.), Graduate School of Arts and Sciences, and Core Research for Evolutional Science and Technology Project of Japan Science and Technology Agency and Bioinformatics Project of Japan Science and Technology Agency (Y.H., H.M., G.M., S.K.), The University of Tokyo, Tokyo 153-8902, Japan; Aska Pharma Medical (S.H.), Kanagawa 213-0934, Japan; and Oncology and Molecular Endocrinology Research Center, Universitaire de Quebec, Quebec G1V 4G2, Canada (D.P.)

Address all correspondence and requests for reprints to: Dr. Suguru Kawato, Professor, Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro, Tokyo 153-8902, Japan. E-mail: kawato{at}phys.c.u-tokyo.ac.jp.

Estradiol (E2) and other sex steroids play essential roles in the modulation of synaptic plasticity and neuroprotection in the hippocampus. To clarify the mechanisms for these events, it is important to determine the respective role of circulating vs. locally produced sex steroids in the male hippocampus. Liquid chromatography-tandem mass spectrometry in combination with novel derivatization was employed to determine the concentration of sex steroids in adult male rat hippocampus. The hippocampal levels of 17β-E2, testosterone (T), and dihydrotestosterone (DHT) were 8.4, 16.9, and 6.6 nM, respectively, and these levels were significantly higher than circulating levels. The hippocampal estrone (E1) level was, in contrast, very low around 0.015 nM. After castration to deplete circulating high level T, hippocampal levels of T and DHT decreased considerably to 18 and 3%, respectively, whereas E2 level only slightly decreased to 83%. The strong reduction in hippocampal DHT resulting from castration implies that circulating T may be a main origin of DHT. In combination with results obtained from metabolism analysis of [3H]steroids, we suggest that male hippocampal E2 synthesis pathway may be androstenedione -> T -> E2 or dehydroepiandrosterone -> androstenediol -> T -> E2 but not androstenedione -> E1 -> E2.






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Copyright © 2009 by The Endocrine Society