The regulation of the 17-deoxy steroids in man.
One must consider the 17-DOS as a biosynthetic pathway with multiple regulatory factors. ACTH is its dominant regulator but in the absence of ACTH and in conditions where plasma renin activity is increased, this biosynthetic pathway maintains its sensitivity to exogenous ACTH. Suppression of the renin system delays the general recovery of aldosterone after the removal of an aldosterone producing adenoma but not of the 17-DOS: a pattern also showed after the removal of a DOC-producing adenoma. In addition to the possible role of the renin system there remain inexplicable situations in its regulation that cannot be explained by ACTH and renin. Our studies suggest that a non-renin, non-ACTH factor may influence the basal production of these steroids, and by its reduction, permits deviation of steroid substrate to cortisol production. This sequence may be operative in the "stress syndrome". Finally, one of the more interesting phenomenonologic patients who has been observed is a young male who has the biochemical findings and clinical signs of DOC excess with hypertension, hyperplasia, suppression of aldosterone and the RAS, and normal cortisol levels. All the 17-DOS are elevated and both adrenal veins have high concentrations. He represents excessive stimulation of this pathway by putative 17-deoxy regulator excess. The renin system is suppressed and ACTH levels are normal. Treatment with suppressive doses of glucocorticoid hormones diminishes the elevated 17-DOS and cortisol and ameliorates blood pressure. In summary, there seems to occur in clinical disorders and contrived experimental settings, suggestions that a non-renin, non-ACTH factor can regulate the 17-DOS, absence can explain some of the unusual conditions described (Fig. 1). The 17-DOS, while a vestigial pathway, may still cause disease, and provide clues to central organization of the adreno-cortical response to injury, stress, and disease.
Biglieri
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EG
University of California Medical Service, San Francisco General Hospital Medical Center.
Irony
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I
Kater
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D000163:Acquired Immunodeficiency Syndrome / Q000097:blood; D000305:Adrenal Cortex Hormones / Q000097:blood / Q000378:metabolism*; D000307:Adrenal Gland Diseases / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D003366:Cosyntropin; D003907:Dexamethasone; D006706:Homeostasis; D006801:Humans; D007018:Hypopituitarism / Q000097:blood* / Q000175:diagnosis; D012016:Reference Values; D013250:Steroid Hydroxylases / Q000378:metabolism; D013312:Stress, Physiological / Q000097:blood; D015383:Zona Fasciculata / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D015415:Biomarkers; D003366:Cosyntropin; D003907:Dexamethasone; D013250:Steroid Hydroxylases