No abstract

Six men and nine women were given intravenous injections of 2.5 mg of metoclopramide to assess its potential as a stimulus to prolactin release. Following the administration of metoclopramide, there was prompt increase in serum prolactin to a peak response of 38.2 +/- 3.9 ng/ml in men and 103 +/- 10.2 ng/ml in women. The prolactin response to metoclopramide in men was compared with the response to 400 mug of TRH in 10 men. The peak response after TRH was 22.4 +/- 2.2 ng/ml, which was significantly less than that observed after metoclopramide. Pretreatment with 500 mg of L-dopa suppressed the prolactin response to metoclopramide in 6 men to a mean response of 16.3 +/- 4.3 ng/ml. We have concluded that metoclopramide is a safe, reliable, and potent stimulus of prolactin secretion and exerts this effect by blocking dopamine receptors in the hypothalamus and decreasing prolactin inhibiting factor. It is free of side effects and is a useful alternative to chlorpromazine.

The effects of dopamine, noradrenaline and 3,4-dihydroxyphenylacetic acid (DOPAC) on the release of prolactin were examined in ovariectomized ewes. Infusion of dopamine (0.5 or 1 microgram/kg per min for 2 h i.v.) reduced plasma prolactin concentrations in a dose-dependent manner, whereas DOPAC (5 or 10 micrograms/kg per min for 2 h i.v.) had no effect. In a further series of experiments, ovariectomized hypothalamopituitary disconnected ewes were given dopamine or noradrenaline (each at 0.5 or 1 microgram/kg per min for 2 h i.v.), and both amines reduced mean plasma concentrations of prolactin with similar potency in a dose-dependent manner. These effects were blocked by treatment with pimozide and prazosin respectively. During the infusion of dopamine, the peripheral plasma concentrations of DOPAC and 3,4-dihydroxyphenylethyleneglycol (DHPG) were increased (DOPAC, 22 +/- 7 (S.E.M.) to 131 +/- 11 nmol/l; DHPG, 2.9 +/- 0.3 to 6.4 +/- 0.2 nmol/l), but plasma concentrations of dopamine and noradrenaline did not change. Finally, administration of domperidone, a specific dopamine receptor antagonist that does not cross the blood-brain barrier, resulted in a sustained increase in plasma prolactin concentrations in ovariectomized ewes. We conclude that the secretion of prolactin from the pituitary gland is under dual inhibitory regulation by both dopamine and noradrenaline in the sheep.

The concentrations of dopamine, noradrenaline and their respective primary neuronal metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and 3,4-dihydroxyphenylethyleneglycol (DHPG) were measured in the hypophysial portal and peripheral plasma of sheep and rats by combined gas chromatography-mass spectrometry. Hypophysial portal and jugular blood samples were taken at 5- to 10-min intervals for 3-7 h from six conscious ovariectomized ewes. Blood was also collected for 30 min under urethane anaesthesia from the cut pituitary stalk from 16 pro-oestrous female and five intact male rats. In ovariectomized ewes, noradrenaline concentrations were higher in hypophysial portal plasma than in peripheral plasma (6.6 +/- 0.8 vs 2.2 +/- 0.4 nmol/l). In contrast, dopamine was undetectable (less than 1 nmol/l) in the portal and peripheral plasma of all ewes. Plasma levels of DOPAC and DHPG in portal and jugular samples were similar. In all pro-oestrous female rats, plasma concentrations of dopamine were higher in portal blood than in jugular blood (8.0 +/- 1.4 vs 4.8 +/- 0.6 nmol/l). Detectable concentrations of dopamine were measured in the portal plasma of two out of five male rats. Noradrenaline concentrations were higher in portal plasma than in peripheral plasma of both female (8.3 +/- 1.7 vs 3.7 +/- 0.6 nmol/l) and male (14.8 +/- 2.7 vs 6.1 +/- 1.2 nmol/l) rats. These data show that noradrenaline, but not dopamine, is secreted into the long portal vessels in sheep. The results suggest that there are species differences in the secretion of hypothalamic dopamine into hypophysial portal blood.