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Regulation of Adrenal Steroidogenesis

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Adrenal Disorders

Part of the book series: Contemporary Endocrinology ((COE))

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Abstract

The human adrenal cortex is divided into concentric zones: the zona glomerulosa produces aldosterone, the zona fasciculata secretes cortisol, and the zona reticularis synthesizes 19-carbon (C19) androgen precursors. Angiotensin II (Ang II) and extracellular K+ are the principal stimuli of aldosterone secretion, whereas adrenocorticotropic hormone (ACTH) is the main stimulus of cortisol and C19 steroid production. Most of the cholesterol used for the biosynthesis of adrenal steroids is derived from receptor-mediated endocytosis of plasma low-density lipoproteins (LDL). In late endosomes, LDL-derived cholesteryl esters (CEs) are hydrolyzed by lysosomal acid lipase. The resultant-free cholesterol can be re-esterified by sterol O-acetyltransferase and stored in lipid droplets. Cholesterol can be liberated from stored CEs by hormone-sensitive lipase, an enzyme activated in response to Ang II or ACTH or stimulation. To initiate steroidogenesis, cholesterol undergoes facilitated transport from a replenishable pool in the outer mitochondrial membrane to the inner mitochondrial membrane, where CYP11A1 catalyzes the conversion of cholesterol to pregnenolone. The remaining steps of steroidogenesis take place in the endoplasmic reticulum and mitochondria. This chapter highlights the regulation of adrenal steroidogenesis. Key intracellular signaling molecules, including second messengers and downstream transcription factors, are reviewed. Pathological conditions associated with aberrant production of adrenal steroids are discussed.

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Acknowledgments

We thank Karin Sanders, Sara Galac, and Audrey Odom John for the assistance with figure preparation. We thank Rebecca Cochran and Paul Hruz for reviewing the manuscript. This work was supported by the Sigrid Jusélius Foundation, the Academy of Finland, Department of Defense grants PC141008 and OC150105, Prostate Cancer Foundation, and the Paulo Foundation.

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Authors and Affiliations

  1. Children’s Hospital, University of Helsinki, Biomedicum Helsinki 2U, Tukholmankatu 8, 00290, Helsinki, Finland

    Marjut Pihlajoki Ph.D.

  2. Children’s Hospital, University of Helsinki, PO Box 22, 00014, Helsinki, Finland

    Markku Heikinheimo M.D., Ph.D.

  3. Departments of Pediatrics and Developmental Biology, Washington University School of Medicine, Box 8208, 660 S. Euclid Ave, St. Louis, MO, 63110, USA

    David B. Wilson M.D., Ph.D.

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  1. Marjut Pihlajoki Ph.D.
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Correspondence to David B. Wilson M.D., Ph.D. .

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  1. Div of Endocrinology and Bone Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA

    Alice C. Levine

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Pihlajoki, M., Heikinheimo, M., Wilson, D.B. (2018). Regulation of Adrenal Steroidogenesis. In: Levine, A. (eds) Adrenal Disorders. Contemporary Endocrinology. Humana Press, Cham. https://doi.org/10.1007/978-3-319-62470-9_2

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