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 hippoc...

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Veröffentlicht in:Endocrinology (Philadelphia) 2009-11, Vol.150 (11), p.5106-5112
Hauptverfasser: Hojo, Yasushi, Higo, Shimpei, Ishii, Hirotaka, Ooishi, Yuuki, Mukai, Hideo, Murakami, Gen, Kominami, Toshihiro, Kimoto, Tetsuya, Honma, Seijiro, Poirier, Donald, Kawato, Suguru
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container_end_page 5112
container_issue 11
container_start_page 5106
container_title Endocrinology (Philadelphia)
container_volume 150
creator Hojo, Yasushi
Higo, Shimpei
Ishii, Hirotaka
Ooishi, Yuuki
Mukai, Hideo
Murakami, Gen
Kominami, Toshihiro
Kimoto, Tetsuya
Honma, Seijiro
Poirier, Donald
Kawato, Suguru
description 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. Improved mass-spectrometric analysis revealed that hippocampal estradiol is mainly synthesized from hippocampus-derived testosterone, and not significantly from circulating testosterone.
doi_str_mv 10.1210/en.2009-0305
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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. 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subjects 17β-Estradiol
Androstenediol
Androstenedione
Animals
Castration
Circulation
Dehydroepiandrosterone
Dihydrotestosterone
Estrone
Female
Gonadal Steroid Hormones - analysis
Gonadal Steroid Hormones - metabolism
Hippocampal plasticity
Hippocampus
Hippocampus - chemistry
Hippocampus - metabolism
Liquid chromatography
Male
Males
Mass spectrometry
Mass spectroscopy
Neuromodulation
Neuroprotection
Rats
Rats, Wistar
Sex
Sex hormones
Steroid hormones
Steroids
Synaptic plasticity
Testosterone
title Comparison between Hippocampus-Synthesized and Circulation-Derived Sex Steroids in the Hippocampus
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