Although
6beta-hydroxycortisol (6betaOHF) 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 6beta-hydroxylating
cortisol, we measured 6betaOHF 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, 6betaOHF 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, 6betaOHF 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 6betaOHF and
cortisol secretion. The 6betaOHF concentration in suprarenal vein samples obtained from the side of
adenomas was markedly increased; the suprarenal vein/inferior vena cava 6betaOHF 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 6betaOHF 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.