Effects of metoclopramide and bromocriptine on prolactin secretion in the pregnant ewe

Metoclopramide and bromocriptine, drugs which are respectively antagonistic and agonistic to dopamine receptor activity, were used to investigate the control of prolactin secretion in the ewe during pregnancy. Normal concentrations of prolactin were found during pregnancy, i.e. values were low and stable during the first 100 days but thereafter increased progressively to reach maximum values at day 140. Treatment with bromocriptine suppressed levels to undetectable values (less than 1.4 micrograms/l plasma) between days 40 and 100 of pregnancy. Later in gestation, however, bromocriptine administered between days 120 and 140 was less effective, indicating that the pituitary gland was less responsive to the same degree of inhibition. Treatment with metoclopramide alone provoked a progressively greater release of prolactin as pregnancy advanced whereas in bromocriptine-treated animals an associated release of prolactin in response to metoclopramide was seen only between days 120 and 140 of pregnancy. These results are interpreted as evidence that the raised concentrations of prolactin characteristic of late pregnancy in the ewe are due to a reduced responsiveness of the pituitary gland to inhibitory stimuli, or to a decreased secretion of endogenous dopamine into the hypophysial portal blood system or to both.