Effect of chronic adrenocorticotropin stimulation on the excretion of 18-hydroxycortisol and 18-oxocortisol.
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.
Gomez-Sanchez
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CE
Department of Medicine, James A Haley Veterans Administration Medical Center, University of South Florida College of Medicine, Tampa 33612.
Clore
J N
JN
Estep
H L
HL
Watlington
C O
CO
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage* / Q000494:pharmacology; D000328:Adult; D000450:Aldosterone / Q000031:analogs & derivatives / Q000652:urine; D001794:Blood Pressure / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000652:urine; D008297:Male; D013268:Stimulation, Chemical; D013760:Tetrahydrocortisol / Q000652:urine; D013761:Tetrahydrocortisone / Q000652:urine
C038135:18-oxocortisol; C018447:aldosterone 18-glucuronide; D000450:Aldosterone; D013761:Tetrahydrocortisone; D013760:Tetrahydrocortisol; D000324:Adrenocorticotropic Hormone; C033689:18-hydroxycortisol; D006854:Hydrocortisone