Glucocorticoid suppression enhances the 18-hydroxycorticosterone and aldosterone response to metoclopramide in man.
18-Hydroxycorticosterone (18-OHB) is a precursor of aldosterone and is the only corticosteroid, other than aldosterone, that is synthesized predominantly in the zona glomerulosa. Administration of the dopamine antagonist, metoclopramide results in parallel rises in plasma 18-OHB and aldosterone levels without affecting the plasma levels of other aldosterone precursors. However, 18-OHB is a product of the zona fasciculata as well as the glomerulosa. Thus, it is possible that metoclopramide may stimulate zona fasciculata secretion of 18-OHB. In order to more selectively examine dopaminergic regulation of zona glomerulosa secretion of 18-OHB we have examined the effect of glucocorticoid suppression of the fasciculata on the 18-OHB and aldosterone responses to metoclopramide, 10 mg iv in 6 normal volunteers. Dexamethasone, 2 mg every 6 hours for 5 days, suppressed basal levels of cortisol, corticosterone, 18-OHB and aldosterone. Dexamethasone treatment had no effect on basal levels of PRA or PRA responses to metoclopramide. The 18-OHB and aldosterone responses to metoclopramide were enhanced (p less than .05) by dexamethasone suppression. The results suggest that dopaminergic mechanisms selectively suppress glomerulosa production of 18-OHB. Endogenous ACTH may inhibit zona glomerulosa production of 18-OHB and aldosterone in response to the dopamine antagonist, metoclopramide.
D015069:18-Hydroxycorticosterone / Q000378:metabolism*; D000328:Adult; D000450:Aldosterone / Q000096:biosynthesis*; D003345:Corticosterone / Q000031:analogs & derivatives*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000037:antagonists & inhibitors; D006801:Humans; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology*; D008875:Middle Aged; D011188:Potassium / Q000097:blood; D011388:Prolactin / Q000097:blood; D012964:Sodium / Q000097:blood
D005938:Glucocorticoids; D000450:Aldosterone; D015069:18-Hydroxycorticosterone; D003907:Dexamethasone; D011388:Prolactin; D012964:Sodium; D008787:Metoclopramide; D011188:Potassium; D003345:Corticosterone