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P450c17—The Qualitative Regulator of Steroidogenesis

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Molecular and Cellular Pediatric Endocrinology

Part of the book series: Contemporary Endocrinology ((COE,volume 10))

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Abstract

The pathways of steroid hormone synthesis are well established, and the molecular identities of the responsible steroidogenic enzymes have been elucidated (Fig. 1) (for review, see refs. 1, 2). The first step in the synthesis of all steroid hormone is the conversion of cholesterol to pregnenolone by the cholesterol side-chain cleavage system, which is found in the mitochondria in the adrenal cortex, gonads, placenta, and brain. Three pairs of electrons from NADPH are passed through a flavoprotein termed ferredoxin reductase (more commonly “adrenodoxin reductase”) to an iron/sulfur protein termed ferredoxin (adrenodoxin) and thence to cytochrome P450scc (where scc denotes side-chain cleavage). P450scc is the enzymatic moiety that binds cholesterol and uses the three pairs of electrons sequentially to catalyze 20α-hydroxylation, 22-hydroxylation, and C20,22 bond scission to yield pregnenolone, which is then rapidly converted to other steroids. The conversion of cholesterol to pregnenolone is the quantitative regulator of steroidogenesis. The chronic, long-term steroidogenic capacity of a cell is determined primarily by transcription of the gene for P450scc, which determines how much P450scc enzyme is present (3). The acute, short-term response of a cell to tropic hormones, which determines how much steroid is released, is determined by the action of the steroidogenic acute regulatory protein (StAR) (4–7).

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  1. Walter L. Miller MD
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Editors and Affiliations

  1. Division of Endocrinology, Children’s Hospital Medical Center, Cincinnati, OH, USA

    Stuart Handwerger MD

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© 1999 Springer Science+Business Media New York

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Miller, W.L. (1999). P450c17—The Qualitative Regulator of Steroidogenesis. In: Handwerger, S. (eds) Molecular and Cellular Pediatric Endocrinology. Contemporary Endocrinology, vol 10. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-697-3_8

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  • DOI: https://doi.org/10.1007/978-1-59259-697-3_8

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4757-5875-7

  • Online ISBN: 978-1-59259-697-3

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