Steroidogenesis in human aldosterone-secreting adenomas and adrenal hyperplasias: effects of hypoxia in vitro.
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.
Raff
Hershel
H
Endocrine Research Laboratory, St.Luke's Medical Center, Medical College of Wisconsin, Milwaukee, WI 53215, USA. hraff@mcw.edu
Bruder
Eric D
ED
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018246:Adrenocortical Adenoma / Q000378:metabolism* / Q000473:pathology; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000450:Aldosterone / Q000096:biosynthesis / Q000378:metabolism*; D015687:Cell Hypoxia; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D003687:Dehydroepiandrosterone / Q000096:biosynthesis; D006801:Humans; D006854:Hydrocortisone / Q000096:biosynthesis; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology; D010100:Oxygen / Q000494:pharmacology; D010313:Partial Pressure; D013256:Steroids / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D013256:Steroids; D003687:Dehydroepiandrosterone; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D010100:Oxygen; D006854:Hydrocortisone