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Steroidogenic Cytochrome P450 Gene CYP11A1: Functions and Regulation

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Fifty Years of Cytochrome P450 Research

Abstract

Steroids belong to the class of endogenous substrates that are metabolized by cytochromes P450. These steroids are produced in our body, mainly from the adrenals and gonads, and circulate throughout the body in minute amounts to exert their physiological functions. The first and rate-limiting step for the production of all steroids is the conversion of cholesterol into pregnenolone, catalyzed by P450scc, or CYP11A1. Deficiency of CYP11A1 results in adrenal insufficiency that can be lethal when untreated. Hypomorphic expression of Cyp11a1 is less detrimental, but still resulted in decreased stress response in mice. CYP11A1 is expressed mainly in the adrenals and gonads, and to a lesser extent brain, skin, and intestine. Transcription factor NR5A1 controls the expression of Cyp11a1 in the adrenals and testis, whereas NR5A2 controls the expression of Cyp11a1 in the intestine. Both NR5A proteins cooperate with other general factors such as Sp1 and AP1 to activate Cyp11a1 expression in response to the stimulation of cAMP. The cyp11a1 mRNA in zebrafish is also deposited as a maternal transcript for the production of pregnenolone in early embryos. Pregnenolone stabilizes microtubules and promotes embryonic cell migration in zebrafish. Thus, use of the zebrafish model reveals a new function of CYP11A1 during early embryogenesis.

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Acknowledgments

Part of the work described in this review was supported by grants NSC 102-2311-B-001-013-MY3 and 102-2923-B-001-003-MY3 from National Science Council, NHRI- EX102-10210SI from National Health Research Institutes, and AS-101-TP-B05 from Academia Sinica, Taiwan.

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Authors and Affiliations

  1. Institute of Molecular Biology, Academia Sinica, Taipei, 115, Taiwan

    Monica Meng-Chun Shih, Hwei-Jan Hsu, Hsin-Chieh Lan, Jui-Hsia Weng, Yu Chien, Meng-Chun Hu & Bon-chu Chung

  2. Department of International Cooperation, National Science Council, Taipei, Taiwan

    Monica Meng-Chun Shih

  3. Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan

    Hwei-Jan Hsu

  4. Graduate Institute of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan

    Hsin-Chieh Lan

  5. Graduate Institute of Physiology, National Taiwan University, Taipei, Taiwan

    Meng-Chun Hu

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  1. Monica Meng-Chun Shih
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Correspondence to Bon-chu Chung .

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    Hiroshi Yamazaki

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Shih, M.MC. et al. (2014). Steroidogenic Cytochrome P450 Gene CYP11A1: Functions and Regulation. In: Yamazaki, H. (eds) Fifty Years of Cytochrome P450 Research. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54992-5_15

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