Regulation of adrenal steroidogenesis

Marjut Pihlajoki, Markku Heikinheimo, David B. Wilson

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

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.

Original languageEnglish
Title of host publicationContemporary Endocrinology
PublisherHumana Press Inc.
Pages15-66
Number of pages52
DOIs
StatePublished - 2018

Publication series

NameContemporary Endocrinology
ISSN (Print)2523-3785
ISSN (Electronic)2523-3793

Keywords

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

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