Comparison between hippocampus-synthesized and circulation-derived sex steroids in the hippocampus.
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 17beta-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 [(3)H]steroids, we suggest that male hippocampal E2 synthesis pathway may be androstenedione --> T --> E2 or dehydroepiandrosterone --> androstenediol --> T --> E2 but not androstenedione --> E1 --> E2.
Hojo
Yasushi
Y
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.
Higo
Shimpei
S
Ishii
Hirotaka
H
Ooishi
Yuuki
Y
Mukai
Hideo
H
Murakami
Gen
G
Kominami
Toshihiro
T
Kimoto
Tetsuya
T
Honma
Seijiro
S
Poirier
Donald
D
Kawato
Suguru
S
D000818:Animals; D005260:Female; D012739:Gonadal Steroid Hormones / Q000032:analysis / Q000378:metabolism*; D006624:Hippocampus / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D012739:Gonadal Steroid Hormones