The peptide oxytocin (OT) is secreted by hypothalamic neurons and exerts numerous actions related to reproduction. OT stimulation of prolactin secretion in female rats is important during the estrous cycle, pregnancy, and lactation. Here we report that OT also stimulates transients of intracellular Ca(2+) concentration in somatotrophs and gonadotrophs as well as the release of GH and LH in a dose-dependent manner with EC50 values that closely correspond to the ligand affinity of the OT receptor (OTR). Remarkably, the hormone-releasing effect of OT in these two cell types is 2 orders of magnitude more sensitive than that in lactotrophs. The specific OTR agonist [Thr(4),Gly(7)]-oxytocin acutely stimulated the release of LH, GH, and prolactin from female rat pituitary cells in primary culture and increased intracellular Ca(2+) concentration in gonadotrophs, somatotrophs, and lactotrophs. In these three cell types, the effects on hormone release and intracellular Ca(2+) of both OT and [Thr(4),Gly(7)]oxytocin were abolished by the specific OT receptor antagonist desGly-NH2-d(CH2)5[D-Tyr(2),Thr(4)]OVT but not by the highly selective vasopressin V1a receptor antagonist, d(CH2)5[Tyr(Me)(2),Dab(5)]AVP. Furthermore, 10 nM arginine vasopressin stimulated LH and GH release comparably with a dose of OT that was at least 10 times lower. Finally, the presence of the OTR-like immunoreactivity could be observed in all three cell types. Taken together, these results show that OT directly stimulates gonadotrophs, somatotrophs, and lactotrophs through OT receptors and suggest that OT signaling may serve to coordinate the release of different pituitary hormones during specific physiological conditions.

Prolactin is an anterior pituitary hormone necessary for fertility, pregnancy maintenance, lactation, and aspects of maternal behavior. In rodents, there is a surge of prolactin on the afternoon of proestrus, and a semi-circadian pattern of prolactin surges during early pregnancy, with a diurnal and nocturnal surge every day. Both of these patterns can be replicated in ovariectomized rats. A prior study demonstrated that central antagonism of κ-opioid receptors, the target of dynorphin, largely abolished the nocturnal prolactin surge in pregnant rats. We build on this to determine whether dynorphin, perhaps from the arcuate population that co-express kisspeptin, neurokinin B, and dynorphin (KNDy neurons), also contributes to the estradiol- or cervical stimulation-induced surges in ovariectomized rats. Ovariectomized rats were treated with either estradiol or cervical stimulation to induce prolactin surge(s). Blood samples were taken around the expected surge time to determine the effect of either acute κ-opioid receptor antagonism or previous chemical ablation of the KNDy population on prolactin levels. Dynorphin antagonism does significantly disrupt the nocturnal prolactin surge, but it does not contribute to the estradiol-induced surge. Chemical ablation of KNDy neurons had opposite effects; ablation of 40 % of the KNDy neurons had no impact on the nocturnal prolactin surge, while a somewhat larger ablation significantly reduced the size of the estradiol-induced surge. We conclude that dynorphin is likely a controlling factor for the nocturnal surge induced by cervical stimulation, and that other KNDy neuron products must play a role in the estradiol-induced surge.

Helena CV, Cristancho-Gordo R, Gonzalez-Iglesias AE, Tabak J, Bertram R, Freeman ME. Systemic oxytocin induces a prolactin secretory rhythm via the pelvic nerve in ovariectomized rats. Am J Physiol Regul Integr Comp Physiol 301: R676 -R681, 2011. First published June 15, 2011 doi:10.1152/ajpregu.00176.2011.-We have shown previously that an intravenous injection of oxytocin (OT) in ovariectomized (OVX) rats initiates a circadian rhythm of prolactin (PRL) secretion similar to that observed after cervical stimulation (CS). In this study, we investigated the pathway through which OT triggers the PRL rhythm. We first tested whether an intracerebroventricular injection of OT could trigger the PRL secretory rhythm. As it did not, we injected OT intravenously while an OT receptor antagonist was infused intravenously. This antagonist completely abolished the PRL surges, suggesting that a peripheral target of OT is necessary for triggering the PRL rhythm. We hypothesized that OT may induce PRL release, which would be transported into the brain and trigger the rhythm. In agreement with this, OT injection increased circulating PRL by 5 min. To test whether this acute increase in PRL release would induce the PRL rhythm, we compared the effect of intravenously administered thyrotropin-releasing hormone (TRH) and OT. Although TRH injection also increased PRL to a comparable level after 5 min, only OT-injected animals expressed the PRL secretory rhythm. Motivated by prior findings that bilateral resection of the pelvic nerve blocks CS-induced pseudopregnancy and OT-induced facilitation of lordosis, we then hypothesized that the OT signal may be transmitted through the pelvic nerve. In fact, OT injection failed to induce a PRL secretory rhythm in pelvic-neurectomized animals, suggesting that the integrity of the pelvic nerve is necessary for the systemic OT induction of the PRL secretory rhythm in OVX rats. oxytocin receptor; pseudopregnancy; lactotrophs MATING OR CERVICAL STIMULATION (CS) induces a circadian rhythm of prolactin (PRL) secretion in female rats, consisting of nocturnal (0300) and diurnal (1700) surges. The rhythm persists for 10 -12 days, which is about half the duration of pregnancy (19). As the rhythm in secretion continues for several days without additional stimuli, it has been suggested that a hypothalamic "memory" is activated by CS and acts to sustain the daily PRL surges (17). This rhythm can be produced in ovariectomized (OVX) rats, demonstrating that the memory does not require ovarian steroids (43). Despite these findings, the mechanism by which the memory is triggered is not understood.PRL secretion by lactotrophs is tonically inhibited by hypothalamic dopamine (DA) (3,11). Whereas the full generation of PRL surges requires a decrease in DA inhibition, the actions of one or more stimulating factors are also needed (16, 18). Several lines of evidence suggest that oxytocin (OT) may act as a PRL-releasing factor to induce PRL surges in several physiological paradigms (23, 39, 40), including mating. Beca...

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