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Regulation of Adrenal Steroidogenesis

  • Marjut Pihlajoki
  • Markku Heikinheimo
  • David B. Wilson
Chapter
Part of the Contemporary Endocrinology book series (COE)

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.

Keywords

Adrenal cortex Adrenal gland Adrenocorticotropic hormone Aldosterone Cortisol Dehydroepiandrosterone Zona glomerulosa Zona fasciculata Zona reticularis 

Notes

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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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Marjut Pihlajoki
    • 1
  • Markku Heikinheimo
    • 2
  • David B. Wilson
    • 3
  1. 1.Children’s Hospital, University of HelsinkiHelsinkiFinland
  2. 2.Children’s Hospital, University of HelsinkiHelsinkiFinland
  3. 3.Departments of Pediatrics and Developmental BiologyWashington University School of MedicineSt. LouisUSA

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