Steroidogenesis in human aldosterone-secreting adenomas and adrenal hyperplasias: effects of hypoxia in vitro. Am J Physiol Endocrinol Metab 2006 Jan;290(1):E199-E203
Date
08/18/2005Pubmed ID
16105860DOI
10.1152/ajpendo.00337.2005Scopus ID
2-s2.0-33644875394 (requires institutional sign-in at Scopus site) 9 CitationsAbstract
The synthesis of adrenal steroids requires molecular oxygen. Because arterial hypoxemia is a common clinical condition, the purpose of the present study was to examine steroidogenesis in vitro under physiological changes in O(2) tension (Po(2)) in cells from human adrenal glands with aldosterone-secreting adenomas (ASA; n=3) or with bilateral adrenal hyperplasia causing Cushing's syndrome (n=4). A decrease in Po(2) from 150 mmHg (mild hyperoxia) to 80 mmHg had minimal effect on steroid production. A reduction to 40 mmHg (still well within the physiological range) significantly inhibited cAMP- and ACTH-stimulated aldosterone, cortisol, and dehydroepiandrosterone (DHEA) production from ASA. Furthermore, cortisol and DHEA production in cells from histologically normal tissue, adjacent to ASA and from bilateral adrenal hyperplasias, was also inhibited under a Po(2) of 40 mmHg. We conclude that physiological decreases in Po(2) to levels typical for adrenal venous Po(2) under mild hypoxia inhibit steroidogenesis. These studies may have implications for oxygen therapy in critically ill patients with functional adrenal insufficiency, as well as for therapeutic options in patients with adrenal neoplasms.
Author List
Raff H, Bruder ED, St. Luke's Medical Center Adrenal Tumor Study GroupAuthor
Hershel Raff PhD Professor in the Academic Affairs department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adrenal GlandsAdrenocortical Adenoma
Adrenocorticotropic Hormone
Aldosterone
Cell Hypoxia
Cells, Cultured
Cyclic AMP
Dehydroepiandrosterone
Humans
Hydrocortisone
Hyperplasia
Oxygen
Partial Pressure
Steroids
Tumor Cells, Cultured