This Article Full Text Full Text (PDF) Supplemental Data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Google Scholar Articles by Munetsuna, E. Articles by Yamazaki, T. PubMed PubMed Citation Articles by Munetsuna, E. Articles by Yamazaki, T.

Retinoic Acid Stimulates 17β-Estradiol and Testosterone Synthesis in Rat Hippocampal Slice Cultures

Laboratory of Molecular Brain Science (E.M., A.I., S.A.J.K., T.Y.) and Department of Behavioral Sciences (M.H.), Graduate School of Integrated Arts and Sciences, Hiroshima University, Higashi-Hiroshima 739-8521, Japan; and Department of Biophysics and Life Sciences (Y.H., H.I., S.K.), Graduate School of Arts and Sciences, University of Tokyo at Komaba, Core Research for Evolutional Science and Technology Project of Japan Science and Technology Agency, University of Tokyo, Meguro, Tokyo 153-8902, Japan

Address all correspondence and requests for reprints to: Takeshi Yamazaki, Graduate School of Integrated Arts and Sciences, Hiroshima University, 1-7-1 Kagamiyama, Higashi-Hiroshima 739-8521, Japan. E-mail: takey{at}hiroshima-u.ac.jp.

The hippocampus is essentially involved in learning and memory processes. Its functions are affected by various neuromodulators, including 17β-estradiol, testosterone, and retinoid. Brain-synthesized steroid hormones act as autocrine and paracrine modulators. The regulatory mechanism underlying brain steroidogenesis has not been fully elucidated. Synthesis of sex steroids in the gonads is stimulated by retinoic acids. Therefore, we examined the effects of retinoic acids on estradiol and testosterone biosynthesis in the rat hippocampus. We used cultured hippocampal slices from 10- to 12-d-old male rats to investigate de novo steroidogenesis. The infant rat hippocampus possesses mRNAs for steroidogenic enzymes and retinoid receptors. Slices were used after 24 h of preculture to obtain maximal steroidogenic activity because steroidogenesis in cultured slices decreases with time. The mRNA levels for P450₁₇, P450 aromatase and estrogen receptor-β in the slices were increased by treatment with 9-cis-retinoic acid but not by all-trans-isomer. The magnitude of stimulation and the shape of the dose-response curve for the mRNA level for P450₁₇ were similar to those for cellular retinoid binding protein type 2, the transcription of which is activated by retinoid X receptor signaling. 9-cis-Retinoic acid also induced a 1.7-fold increase in the protein content of P450₁₇ and a 2-fold increase in de novo synthesis of 17β-estradiol and testosterone. These steroids may be synthesized from a steroid precursor(s), such as pregnenolone or other steroids, or from cholesterol, as so-called neurosteroids. The stimulation of estradiol and testosterone synthesis by 9-cis-retinoic acid might be caused by activation of P450₁₇ transcription via retinoid X receptor signaling.

This article has been cited by other articles:

				Y. Hojo, S. Higo, H. Ishii, Y. Ooishi, H. Mukai, G. Murakami, T. Kominami, T. Kimoto, S. Honma, D. Poirier, et al. Comparison between Hippocampus-Synthesized and Circulation-Derived Sex Steroids in the Hippocampus Endocrinology, November 1, 2009; 150(11): 5106 - 5112. [Abstract] [Full Text] [PDF]