The vasopressin-associated glycopeptide is not a prolactin-releasing factor: studies with lactating Brattleboro rats

We have recently reported that the posterior pituitary contains PRL-releasing factor (PRF), a small (less than 5000 mol wt) peptide which induces a rapid, hormone-specific, and concentration-dependent stimulation of PRL secretion. Although the identity of posterior pituitary PRF is yet unknown, it is distinct from known PRL secretagogues. Recently, the vasopressin-associated glycopeptide (VAG), which is concentrated in the posterior pituitary, was suggested as a PRF. To investigate whether VAG functions as a PRF, we used Brattleboro rats, which are deficient in arginine vasopressin (AVP), AVP-associated neurophysin, and VAG. Homozygous (DI) and heterozygous (HZ) lactating Brattleboro rats were used. The water consumption of pregnant DI rats (greater than 300 ml/day) was 6-fold higher than that of HZ rats. To correct their water imbalance, DI rats were implanted with osmotic minipumps containing the vasopressin analog 1-desamino-8-D-arginine vasopressin. On days 7-8 of lactation, pups were separated for 6 h, and blood was collected from the dams via a jugular cannula. Upon introduction of the pups, plasma PRL levels increased 100-fold in both DI and HZ rats and remained elevated for the duration of suckling. The suckling-induced rises in plasma oxytocin in DI and HZ rats were also superimposable. The weight gains of the pups of DI and HZ mothers were similar. PRF activity was determined using perifused anterior pituitary cells. Posterior pituitaries from DI and HZ rats contained equivalent amounts of PRF activity. Moreover, purified rat VAG (1.5 and 6.0 micrograms) failed to stimulate PRL release from pituitary cells. The posterior pituitary content of immunoreactive AVP was 2500-fold higher in HZ rats, but the contents of dopamine and oxytocin were similar. It is concluded that VAG neither mediates the suckling-induced rise of plasma PRL, nor stimulates PRL secretion from perifused anterior pituitary cells. Furthermore, posterior pituitaries from DI and HZ rats contain equivalent amounts of PRF activity. Collectively, these data indicate that VAG is not the posterior pituitary PRF.