Studies on the central and peripheral dopaminergic control of PRL secretion in man: failure to demonstrate the existence of a dopamine-mediated prolactin-inhibiting factor.

Abstract

The existence of a putative central prolactin-inhibiting factor (PIF) distinct from dopamine (DA) but dependent on DA mechanisms for release has been suggested from recent animal studies. We investigated the possibility of the existence of such a PIF in man by combining the use of monoiodotyrosine (MIT), an inhibitor of central DA synthesis, domperidone, a DA receptor antagonist that does not enter the blood-brain barrier and DA itself. 6 normal volunteers underwent three sets of studies: (1) PRL stimulation test to 400 micrograms TRH i.v., 1 g MIT orally or 5 mg domperidone i.v., (2) peripheral DA receptor blockade study in which either domperidone, MIT or TRH was administered at 120 min during a 240-min domperidone infusion (50 micrograms/min) which was preceded by a 5-mg bolus dose of domperidone i.v. and, (3) DA infusion study in which MIT was administered at 120 min during a 240-min infusion of DA in a dose (0.5 microgram/kg X min) known to elevate peripheral DA concentration to levels reported for pituitary portal plasma. In the PRL stimulation tests, the mean +/- SE peak response was significantly greater (p less than 0.002) with domperidone (3,900 +/- 840 mIU/l) than with MIT (1,880 +/- 400 mIU/l) or TRH (2,094 +/- 450 mIU/l). In the peripheral DA receptor blockade study the initial domperidone-induced PRL response was not sustained during the domperidone infusion. Neither a second dose of domperidone nor MIT administration at 120 min resulted in a significant release of PRL.(ABSTRACT TRUNCATED AT 250 WORDS)