On the role of dopamine receptors in the central regulation of human TSH.

The effects of acute administration of haloperidol (4 mg im) and pimozide (4 mg orally) on TSH and Prl secretion were studied in normal and hypothyroid man. The TRH-induced TSH secretion before and after pre-medication with pimozide and domperidone, a peripheral dopamine (DA) blocker, was also evaluated in a group of normal subjects. Haloperidol and pimozide induced a marked increment in serum Prl; mean Prl levels were still significantly elevated 12 h following pimozide administration. A small but significant TSH increase was observed following haloperidol and pimozide in normal as well as hypothyroid subjects. Both domperidone and pimozide significantly enhanced TRH-induced TSH release. In another experiment 3 women with primary thyroid failure received an infusion of DA (4 micrograms/kg/min for 4 h) with and without domperidone administration. TSH and Prl levels were suppressed by DA, but the effect was completely abolished by domperidone. The results suggest that psychotrophic drugs, such as haloperidol and pimozide, can, like substituted benzamides, stimulate TSH release in man. Since domperidone and DA do not cross the blood-brain-barrier and domperidone significantly enhanced the TSH response to TRH, the data also support the hypothesis that human TSH is regulated by DA at the hypothalamus (median eminence) and/or pituitary level.