We have previously reported that neurokinin A (NKA), a tachykinin closely r
elated to substance P, increases the release of prolactin (PRL) from the an
terior pituitary gland of male rats, but not from pituitaries of ovariectom
ized (OVX) female rats. In this study, we evaluated the influence of estrog
ens in the action of NKA. on PRL secretion in female rats. NKA stimulated t
he in vitro release of PRL from pituitary glands of OVX-chronically estroge
nized rats, and of proestrus and estrus rats, but had no effect in anterior
pituitaries of diestrus rats. In addition, we observed that cultured anter
ior pituitary cells of OVX rats responded to NKA only when they were incuba
ted for 3 days in the presence of estradiol 10(-9) M. This effect was block
ed by L-659,877, an NK-2 receptor antagonist. We also studied the action of
NKA on PRL, release during lactation. The response of anterior pituitary c
ells to NKA was variable over this period. The maximal sensitivity to NKA w
as observed at day 10 of lactation. Furthermore, the blockade of endogenous
NKA by the administration of an anti-NKA serum to lactating rats reduced t
he PRL surge induced by the suckling stimulus. These results show that the
responsiveness of the anterior pituitary gland of female rats to NKA is mod
ulated by the endocrine environment, and suggest that NKA may participate i
n the control of PRL secretion during the estrus cycle and lactation.