Antagonism of Oxytocin Prevents Suckling- and Estradiol-Induced, But Not Progesterone-Induced, Secretion of Prolactin

In female rats, estradiol (E-2) and suckling induce prolactin (PRL) secretion. This involves inhibition of hypothalamic dopaminergic tone and stimulation by a PRL-releasing hormone, possibly oxytocin (OT). Infusing an OT antagonist (OTA) iv, we evaluated the role of OT on suckling- and E-2-induced PRL secretion. Three days after parturition at 0900 h, lactating dams were fitted with 24-h osmotic minipumps filled with saline or OTA. On d 5 of lactation, pups were separated from their dams for 6 h. Immediately or 20 min after the resumption of suckling, dam trunk blood was collected. Also, ovariectomized (OVX) rats were treated with E-2 (OVE) and OTA at 1000 h on d 1. Blood samples were obtained from 1300 to 2100 h on d 2 for PRL measurements. Additionally, OVX rats were evaluated on d 2 after receiving progesterone (P-4). OTA blocked suckling and E-2-induced release of PRL but not that induced by E-2+P-4. Pups from treated dams failed to gain weight when allowed to nurse for 20 min on d 5 but gained more than 7 g when nursed on d 7 of lactation, indicating that the OTA was active 48 h later. Western blot analysis showed that E-2 treatment increased OT receptors in the anterior pituitary when compared with OVX animals. No further increase was observed in response to the P-4, suggesting that the enhancing effect of P-4 on E-2-induced PRL release may act through mechanisms independent of OT. These data demonstrate the role of OT in the control of suckling and steroid-induced PRL secretion. (Endocrinology 150: 2292-2299, 2009)