| Title | Retinoic acid stimulates 17{beta}-estradiol and testosterone synthesis in rat hippocampal slice cultures. | | Author(s) | Munetsuna E, Hojo Y, Hattori M, Ishii H, Kawato S, Ishida A, Kominami SA, Yamazaki T | | Institution | Laboratory of Molecular Brain Science, Graduate School of Integrated Arts and Sciences, Hiroshima University, 1-7-1 Kagamiyama, Higashi-Hiroshima 739-8521, Japan; Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, the University of Tokyo at Komaba, Core Research for Evolutional Science and Technology Project of Japan Science and Technology Agency, The University of Tokyo, Meguro, Tokyo 153-8902, Japan; Department of Behavioral Sciences, Graduate School of Integrated Arts and Sciences, Hiroshima University, 1-7-1 Kagamiyama, Higashi-Hiroshima 739-8521, Japan. | | Source | Endocrinology 2009 Jun 4. | | Abstract | The hippocampus is essentially involved in learning and memory processes. Its functions are affected by various neuromodulators, including 17beta-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 10-12-day-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 hours of pre-culture to obtain maximal steroidogenic activity, because steroidogenesis in cultured slices decreases with time. The mRNA levels for P45017alpha, P450arom and estrogen receptor beta 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 P45017alpha were similar to those for cellular retinoid binding protein type-2, 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 P45017alpha, and a 2-fold increase in de novo synthesis of 17beta-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 P45017alpha transcription via retinoid X receptor signaling. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19497980 |
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