Arginine vasopressin exerts opposing effects on milk ejection via oxytocin and vasopressin V1a receptors in mice

Milk ejection is the final process in maternal milk transfer from mothers to offspring and is regulated by oxytocin (OT) released from the neurohypophysis in response to the milk ejection reflex. Arginine vasopressin (AVP), another neurohypophyseal hormone well known for its antidiuretic and vasoconstrictive effects, shares structural similarity with OT, and intravenous AVP injection can also induce milk ejection. Nonetheless, AVP has also been reported to inhibit OT-induced milk ejection in rabbits. In this study, we examined the roles of OT and AVP receptors in these opposing effects of AVP on milk ejection using an in vivo assay model in mice. AVP induced milk ejection and this effect was inhibited by an OT receptor antagonist. Intravenous pretreatment with AVP suppressed the following transient milk ejection induced by intravenous OT injection. Furthermore, AVP treatment interrupted the continuous milk ejection induced by intraperitoneal OT. These inhibitory effects of AVP were ameliorated by pretreatment with a selective Avpr1a antagonist. We further examined the role of AVP receptors using Avpr1a and Avpr1b knockout mice. The AVP-dependent inhibition of OT-induced milk ejection was abolished in Avpr1a knockout mice, but not in Avpr1b knockout mice. Our findings suggest that AVP induces milk ejection through the OT receptor while inhibiting OT-induced milk ejection via Avpr1a. This duality might reflect a physiological mechanism for restricting milk transfer under severe stress or hyperosmotic conditions and could provide insights into breastfeeding difficulties in humans, including the perception of insufficient milk and infant failure to thrive.