Effect of chronic adrenocorticotropin stimulation on the excretion of 18-hydroxycortisol and 18-oxocortisol

• Published in: The journal of clinical endocrinology and metabolism Vol. 67; no. 2; p. 322
• Main Authors: Gomez-Sanchez, C E, Clore, J N, Estep, H L, Watlington, C O
• Format: Journal Article
• Language: English
• Published: United States 01.08.1988
• Subjects: Adrenal Glands - drug effects; Adrenal Glands - metabolism; Adrenocorticotropic Hormone - administration & dosage; Adrenocorticotropic Hormone - pharmacology; Adult; Aldosterone - analogs & derivatives; Aldosterone - urine; Blood Pressure - drug effects; Humans; Hydrocortisone - analogs & derivatives; Hydrocortisone - urine; Male; Stimulation, Chemical; Tetrahydrocortisol - urine; Tetrahydrocortisone - urine
• ISSN: 0021-972X
• DOI: 10.1210/jcem-67-2-322

The human adrenal gland can metabolize cortisol to yield steroids oxygenated at the 18 position in a series of reactions similar to those by which corticosterone is converted to 18-hydroxycorticosterone and aldosterone and perhaps catalyzed by the same enzyme. These analog steroids, 18-hydroxycortisol and 18-oxocortisol, are produced in small quantities normally, but can be produced in excess by aldosterone-producing adrenal adenomas and in glucocorticoid-suppressible aldosteronism. Chronic ACTH administration has been reported to produce a transient increase in aldosterone production. We studied the effect of chronic ACTH administration on the excretion of aldosterone-18-oxoglucuronide and its relationship to the excretion of 18-hydroxycortisol and 18-oxocortisol. Five normal men collected 24-h urine samples for 3 control days and 5 days while receiving ACTH (40 U, im, twice daily). Urinary excretion of tetrahydrocortisol, tetrahydrocortisone, aldosterone 18-oxo-glucuronide, 18-hydroxycortisol, and 18-oxo-cortisol was measured by RIA. Urinary tetrahydrocortisol and tetrahydrocortisone excretion increased 7- to 10-fold during ACTH administration. Urinary aldosterone 18-oxoglucuronide excretion increased to a peak on the second day (6-fold increase) and decreased to basal levels by the fifth day of continuous ACTH administration. The excretion of 18-hydroxycortisol increased about 6-fold and remained elevated throughout the period of ACTH administration. The excretion of 18-oxocortisol increased from an average of 3.7 nmol/day to a peak of 176.7 nmol/day (a 47-fold increase) on the third day and decreased to 107.9 nmol/day on the fifth day of ACTH administration. These results are consistent with the hypothesis that the decrease in aldosterone production after 2 days of ACTH administration is the result of induction of 17-hydroxylase by ACTH, resulting in the biosynthesis of cortisol in these cells. Since the cells have the cytochrome P-450-dependent corticosterone methyl oxidase enzyme, cortisol becomes its predominant substrate, resulting in the increase in 18-hydroxycortisol and 18-oxocortisol production. We have called these cells transitional cells because they have enzymatic systems of the zona glomerulosa and the zona fasciculata.