Role of oxytocin on prolactin secretion during proestrus and in different physiological or pharmacological paradigms.
The present study was designed to evaluate the possible physiological role of oxytocin (OXY) on PRL release by examining the effect of administration of potent pharmacological antagonists of OXY on the stimulation of PRL secretion observed in vitro from anterior pituitary (AP) cells in response to OXY administration or in a number of in vivo paradigms. OXY caused a dose-related increase in PRL release from dispersed AP cells and short term AP cell cultures which was blocked by administration of the OXY antagonists [1-deaminopenicillamine, 2-O-methyltyrosine, 8-ornithine]vasotocin (dPOMeOVT) or [1-(beta-mercapto-beta,beta-cyclopentamethylene propanoic acid)2-O-methyltyrosine, 8-ornithine]vasotocin (MPOMeOVT), respectively. The antagonists were given in vivo in a dose that completely blocked suckling-induced milk let-down for up to 90 min. Injection of the antagonists did not alter the 5-hydroxytryptophan-induced increase in plasma PRL or the increase associated with acute ether stress or acute suckling stimuli, suggesting that OXY is not a major component involved in the neuroendocrine mechanisms responsible for those particular increases. On the other hand, iv administration of dPOMeOVT or MPOMeOVT prevented the increase in plasma PRL normally observed on the afternoon of proestrus in the cycling female rat. The characteristic surge of LH was also blocked by high doses of these antagonists. These data demonstrate that PRL secretion undergoes a differential regulation, in that OXY appears to play a major role in regulating the increase in plasma PRL observed on the afternoon of proestrus, but apparently provides little, if any, contribution toward the neuroendocrine regulation of the increases in PRL associated with 5-hydroxytryptophan administration, acute ether stress stimulus, or acute suckling stimulus. The data also suggest that OXY receptors located in the AP that are involved in the OXY-induced increase in PRL release may be similar to those OXY receptors located in mammary and uterine tissue, since specific biological effects of OXY in those tissues are effectively blocked by the OXY antagonists dPOMeOVT and MPOMeOVT. A possible role of OXY neurons in the neural mechanisms triggering the LH surge during proestrus is also suggested.