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

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 less than 0.01) and 2- to 3-fold (P less than 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 less than 0.01) into the medium as paired controls, but 10(-7) M OT was ineffective. The iv injection of 1 or 10 micrograms OT into conscious male rats elevated plasma PRL by 50% (P less than 0.05) or 500% (P less than 0.001), respectively, above basal values at 5 min only. Vehicle or 0.1 microgram OT were without effect. When 0.1 microgram OT was microinjected into the third ventricle (3V) of conscious male rats, it paradoxically reduced plasma PRL by 40% at 30 min (P less than 0.05), whereas 1 microgram OT significantly lowered PRL at 5-60 min, with the maximum suppression (60%, P less than 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 microgram only) elevated (P less than 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.

Pituitary Portal Plasma Levels of Oxytocin during the Estrous Cycle, Lactation, and Hyperprolactinemia

“…Exogenous OT administration is known to stimulate PRL secretion both in vivo and in vitro, [5][6][7][8][9] Oxytocin receptors have been identified in the anterior pituitary gland. Two pharmacologically distinct types of OT receptors have been characterized in this gland.…”

“…Recently, new OT-containing fiber systems have been identified in the median eminence [1][2][3][4] and have been implicated in the control of prolactin (PRL) and adrenocorticotropin (ACTH) secretion from the anterior lobe of the pituitary gland. [5][6][7][8][9][10][11][12] This paper summarizes experimental findings that evaluate the hypophysiotropic function of median eminence OT by characterizing neuropeptide secretion into the blood of pituitary portal vessels under physiological conditions when the secretion of PRL is known to be altered.…”

Effect of oxytocin infusion on secretion of progesterone and luteinizing hormone and the concentration of uterine oxytocin receptors during the periovulatory period in cloprostenol-treated ewes

“…More recent work on rodents has shown that treatment of pro-oestrous rats with oxytocin or its antagonists in vivo can influence LH release (Johnston & Negro-Villar, 1988;Robinson & Evans, 1990) and oxytocin also acted as a releasing agent for LH from rat pituitary cells in vitro, an effect that could be blocked by co-administration of an oxytocin antagonist (Evans & Catt, 1989;Evans et al, 1989). These studies suggest that endogenous oxytocin could be of physiological importance in the regulation of the LH surge, but other workers have treated rats with either oxytocin or an oxytocin antiserum and reported no change in LH release (Lumpkin et al, 1983;Sarker, 1988). This relationship has not been investigated in detail in ewes, although Sheldrick & Flint (1990) found that a relatively low dose (3 nmol h~1) oxytocin infusion had no effect on LH secretion during the luteal phase.…”

Vasoactive intestinal polypeptide modulates the estradiol-induced prolactin surge by entraining oxytocin neuronal activity

“…Many PRH candidates have been suggested, but overwhelming evidence suggests oxytocin (OT) as the main PRH. The cell membrane of lactotrophs bear OT receptors (Chadio and Antoni, 1989), administration of OT stimulates PRL secretion (Chadio and Antoni, 1993;Lumpkin et al, 1983;Salisbury et al, 1980;Samson et al, 1989) and antagonism of OT prevents PRL release (Arey and Freeman, 1989;Arey and Freeman, 1990;Johnston and Negro-Vilar, 1988;McKee et al, 2007;Sarkar, 1988). Estradiol also influences OT synthesis (Breton et al, 1995) and secretion (Yamaguchi et al, 1979), suggesting an additional permissive role of E 2 on PRL secretion via control of OT.…”