AUTOPARACRINE ACTION OF VASOACTIVE-INTESTINAL-PEPTIDE ON DOPAMINERGICCONTROL OF PROLACTIN SECRETION

We have previously reported that pituitary vasoactive intestinal pepti de (VIP) mediates through autoparacrine mechanisms insulinlike growth factor-I and TRH-stimulated PRL release. In the present study, we have investigated whether VIP might also be implicated in the PRL increase that follows dopamine (DA) withdrawal. The experiments were carried o ut in defined medium supplemented or not with T-3, as in a previous st udy we had found that PRL release increases under low T-3 culture cond itions due to mediation by concomittant stimulus of VIP. Anterior pitu itary (AP) cells from adult male rats were incubated for 1 h in the pr esence of DA (10 mu M), a VIP-receptor antagonist (VIP-At) (200 nM), o r DA plus VIP-At. Then media were removed and the cells were washed wi th PBS and reincubated under the same conditions but without the addit ion of DA. In the first incubation, DA inhibited PRL release by 80%, a nd VIP release by 20% in both T-3-free and T-3 medium. In the second p eriod of incubation, PRL and VIP release were increased in AP cells pr eviously exposed to DA. These effects were greater when the cells were cultured in T-3-free medium than in T-3-medium (225% and 150%, respec tively for PRL release; and 155 and 135%, respectively for VIP release ). PRL response to DA withdrawal was inhibited by the simultaneous pre sence of VIP-At. This inhibition was again greater when the cells were incubated in medium supplemented with T-3. Thus, the stimulus of DA w ithdrawal was inhibited by 88% in T-3-free medium and by 37% in T-3-me dium. To investigate whether pituitary VIP messenger RNA (mRNA) expres sion is under dopaminergic control, AP cells were incubated in the pre sence or absence of bromocriptine (BC) (10 nM) for 2 and 24 h. After 2 4 h of incubation, BC decreased mRNA levels of PRL and of the two tran scripts which VIP expresses in AP. As with DA, BC also inhibited PRL a nd VIP release both at 2 and 24 h. These data demonstrate that VIP, at least partially, mediates DA withdrawal-induced PRL release through a n autoparacrine action. They also suggest that simultaneous inhibition of pituitary VIP mRNA expression and VIP release may be a necessary m echanism for the dopaminergic inhibition of PRL mRNA expression and PR L release.