Submitted on July 25, 2005
Accepted on August 13, 2005
Steroidogenesis in Human Aldosterone-Secreting Adenomas and Adrenal Hyperplasias: Effects of Hypoxia in vitro
Hershel Raff1* and Eric D Bruder1
1 Endocrine Research Laboratory, St. Luke's Medical Center, Medical College of Wisconsin, Milwaukee, WI, USA
* To whom correspondence should be addressed. E-mail: hraff{at}mcw.edu.
The synthesis of adrenal steroids requires molecular oxygen. Since arterial hypoxemia is a common clinical condition, the purpose of the present study was to examine steroidogenesis in vitro under physiological changes in O2 tension (PO2) 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 PO2 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 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 PO2 of 40 mmHg. We conclude that physiological decreases in PO2 to levels typical for adrenal venous PO2 under mild hypoxia, inhibits 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.
