Commentary: Extra-Adrenal Corticosteroid Biosynthesis

Celso E Gomez-Sanchez and Elise P Gomez-Sanchez
Endocrinology, Volume 163, Issue 4, April 2022, bqac016
https://doi.org/10.1210/endocr/bqac016

Abstract

The glucocorticoids (GCs) corticosterone and cortisol and the mineralocorticoid aldosterone are synthesized and secreted from the adrenal gland into the circulation and then transported to their target organs where they exert their actions. Circulating GC concentrations are primarily regulated by the hypothalamic-pituitary axis and those of aldosterone by the renin-angiotensin system. Adrenalectomy almost totally eliminates them from the circulation; however, very low levels of corticosterone and aldosterone are detected in the circulation and select tissues in adrenalectomized rats. De novo extra-adrenal biosynthesis of corticosterone and aldosterone from cholesterol has been described in several organs and is postulated to have a paracrine role in physiology, while contributing negligibly to blood levels. Due to significant sequestration of circulating corticosteroids within target tissues, validation of de novo synthesis requires demonstration of the expression of meaningful quantities of StAR protein and all requisite steroidogenic enzymes including CYP11B1 for cortisol and corticosterone and CYP11B2 for aldosterone by quantitative reverse transcription-polymerase chain reaction, Western blot, and/or immunohistochemistry; biosynthesis from labeled precursors; measurement of steroids in the tissues after adrenalectomy; and circumscribed delivery of specific steroidogenic enzyme inhibitors to where steroidogenesis is postulated to occur to determine its physiological relevance.

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