Hypothalamic and Pituitary Sites of Action of Oxytocin to Alter Prolactin Secretion in the Rat*

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Abstract
To determine whether oxytocin (OT) could alter the release of PRL and other hormones from the anterior pituitary gland, the effects of OT were examined in two in vitro and two in vivo test systems. Cells dispersed from anterior pituitary glands of intact adult male rats were incubated in medium containing OT at doses of 10-8, 10-7, 10-6, and 10-5 M in two trials. OT stimulated PRL release 1.5-fold (P < 0.01) and 2- to 3-fold (P < 0.001) above control levels at 10-8 and 10-7 M doses, respectively, thus indicating a dose-dependent relationship. Higher doses did not produce a further elevation above that obtained with 10-7 M OT. Arginine vasopressin (AVP) caused a slight decrease in PRL release from dispersed cells while TRH produced a small (25%), significant, but nondose-related increase in PRL release. Hemipituitary glands from adult male rats, incubated with 10-6 and 10-5 M OT, released twice as much PRL (P < 0.01) into the medium as paired controls, but 10-7 M OT was ineffective. The iv injection of 1 or 10 fig OT into conscious male rats elevated plasma PRL by 50% (P < 0.05) or 500% (P < 0.001), respectively, above basal values at 5 min only. Vehicle or 0.1 μg OT were without effect. When 0.1 μg OT was microinjected into the third ventricle (3V) of conscious male rats, it paradoxically reduced plasma PRL by 40% at 30 min (P < 0.05), whereas 1 μg OT significantly lowered PRL at 5–60 min, with the maximum suppression (60%, P < 0.001) occurring at 30 min. These latter findings may indicate that an ultrashort loop feedback mechanism exists whereby exogenous OT decreases hypothalamic OT secretion, thereby reducing the OT stimulus for PRL release. The specificity of the OT effect on PRL was attested to by the failure of OT to alter significantly FSH, LH, and TSH in each system. GH was unchanged except that 3V-injected OT (1 μg only) elevated (P < 0.001) plasma GH at 15–30 min. These results support the view that OT acts directly on the cells of the anterior pituitary gland at low to high doses to release PRL specifically and in a dose-related fashion. In contrast, 3V injection of OT reduces PRL secretion, thereby suggesting that OT may decrease its own neurosecretion by ultrashort loop feedback and thus reduce an OT stimulus for PRL release.