ACTH-mediated effect of metoclopramide on plasma pregnenolone in man

Five healthy adult men were given metoclopramide (10 mg and 20 mg) iv and the effects of L-dopa and dexamethasone on metoclopramide-induced increases in the plasma pregnenolone concentration were determined. After an injection of 10 mg metoclopramide, the pregnenolone level rose slightly, though not significantly vs a control. After injecting 20 mg metoclopramide, the pregnenolone level rose significantly vs both the control and the basal level. The pregnenolone increase was not inhibited by L-dopa pretreatment, whereas pretreatment with dexamethasone did suppress it significantly. The data suggest that metoclopramide increases pregnenolone secretion through an ACTH-dependent effect and that dopamine does not modulate pregnenolone secretion in man. This means that dopaminergic modulation does not affect the early steps (cholesterol to pregnenolone) of steroid biosynthesis in man.