Secretion of Hydroxycortisol by Adrenals
Secretion of 6-hydroxycortisol by normal human adrenals and adrenocortical adenomas
Nikolette Szcs, Ibolya Varga, Attila Patócs, Miklós Tóth, Edit Gláz and Károly Rácz,
Gastroenterological and Endocrinological Research Group, 2nd Department of Medicine, Faculty of Medicine, Semmelweis University, Szentkirályi 46, Budapest H-1088, Hungary
Received 21 January 2003; revised 27 March 2003; accepted 1 April 2003. ; Available online 3 June 2003.
Abstract
Although 6-hydroxycortisol (6OHF) is usually considered a cortisol metabolite produced by the liver, a few reports suggest that it may also originate from extrahepatic sources. To examine whether human adrenal cells are capable of 6-hydroxylating cortisol, we measured 6OHF secretion with a radioimmunoassay method in isolated human adrenal cell systems obtained from three normal adrenals, four nonhyperfunctioning adrenocortical adenomas, two adrenal adenomas causing Cushing's syndrome, and five aldosterone (Aldo)-producing adenomas. Cells were examined both under basal conditions and after stimulation with adrenocorticotrophic hormone (ACTH). In addition, 6OHF concentrations were determined in inferior vena cava and suprarenal vein plasma samples obtained from the side of nonhyperfunctioning adrenal adenomas (five patients) and aldosterone-producing adenomas (five patients). Under basal incubation conditions, 6OHF secretion, expressed as a percent of cortisol secretion, was between 0.5 and 2.0% in normal adrenal cells, between 1.0 and 7% in cells from nonhyperfunctioning adenomas, 12 and 15% in cells from Cushing's syndrome patients, and between 2.6 and 3.9% in cells from aldosterone-producing adenomas. In these cells, increasing doses of ACTH produced a dose-dependent stimulation of both 6OHF and cortisol secretion. The 6OHF concentration in suprarenal vein samples obtained from the side of adenomas was markedly increased; the suprarenal vein/inferior vena cava 6OHF ratios were 13.1±2.1 (mean±S.E.) in the case of nonhyperfunctioning adenomas and 17.8±4.5 in the case of aldosterone-producing adenomas. These results firmly suggest that 6OHF is not only a hepatic metabolite, but also a secretory product of human adrenals and that similarly to cortisol, its secretion may be controlled by ACTH.
Author Keywords: 6-Hydroxycortisol; Cortisol; Human adrenal gland; Adrenocortical adenoma cells; Corticosteroid biosynthesis
Corresponding author. Tel.: +361-266-0926; fax: +361-266-0816.