Abstract
Although removal of dopamine inhibition is established as a major factor in prolactin (PRL) release, a large body of evidence suggests that hypothalamic oxytocin (OT) may serve as a PRL-releasing hormone in the rat. PRL release is modulated by estradiol (E2), which rises between diestrus and proestrus of the estrous cycle, causing a PRL surge in the afternoon of proestrus. Given that E2 strongly modulates OT actions in both central and peripheral tissues, OT action on lactotrophs might also be modulated by the stage of the estrous cycle. To test this hypothesis, we have monitored PRL release and intracellular calcium levels ([Ca(2+)](i)) induced by OT in pituitary lactotrophs obtained from female rats in either diestrus 1 or proestrus. We found that both secretory and [Ca(2+)](i) responses to OT are significantly increased in lactotrophs obtained on proestrus. Moreover, we show that these differences are due to an increase in both the number of OT-responding lactotrophs and the magnitude of their individual [Ca(2+)](i) responses. Both secretory and [Ca(2+)](i) responses were abolished by a specific OT antagonist. Finally, dose-dependent studies show that the increased PRL-releasing effect of OT on proestrus is significant over a wide range of concentrations, particularly those observed in hypophyseal portal plasma. These results suggest that the rising E2 titers that culminate on proestrus facilitate the stimulatory action of OT on lactotrophs and support the notion that OT is a PRL-releasing hormone with an important role in the production of the proestrous surge of PRL.