Systemic oxytocin induces a prolactin secretory rhythm via the pelvic nerve in ovariectomized rats

Abstract

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...

Distinct BOLD Activation Profiles Following Central and Peripheral Oxytocin Administration in Awake Rats

“…Ramos and colleagues measuring social behavior in rats used similar doses of OT (0.1, 0.25, 0.5, and 1.0 mg/kg) given IP and failed to show a clear dose-response as only the 0.5 mg/kg dose had any significant effect (Ramos et al, 2013 ). The low dose of 0.1 mg/kg and high dose of 2.5 mg/kg used in our study brackets much of the behavioral literature although there are reports of behavioral effects with as little as 0.1–5.0 μg/kg of OT (Moody et al, 1994 ; Missig et al, 2010 ; Helena et al, 2011 ), a 1000-fold less than reported in most studies. OT has a very high binding affinity for its receptor (<0.5 nM) and the range of doses reported in the literature following systemic administration would easily engage the receptors – both central and peripheral, if the target could be reached.…”

Cervical stimulation activates A1 and locus coeruleus neurons that project to the paraventricular nucleus of the hypothalamus

“…It was also shown that blocking OT receptors prohibits suckling- and E 2 -induced PRL secretion [30]. Most notably, a bolus injection of OT initiates CS-like PRL surges [5] and this OT signal is transmitted through the pelvic nerve [24]. Cervical stimulation activates OT neurons in the PVN blocking peripheral OT receptors prevents CS-induced PRL secretion [38].…”

Hypothalamic Control of Prolactin Secretion, and the Multiple Reproductive Functions of Prolactin

“…359 Regulation of oxytocin neurons: Oxytocin neurons play a critical role in parturition, milk ejection, and maternal behavior. 321,694 In lactating animals, prolactin stimulates oxytocin secretion 695,696 and expression of oxytocin mRNA, 697,698 likely involving the JAK-STAT pathway to activate gene transcription. 574,689,690 In contrast, prolactin appears to increase the secretion of oxytocin in males 691 and ovariectomized females, 692 likely through activation of neuronal nitric oxide synthesis.…”