PARA-CHLOROPHENYLALANINE TREATMENT INHIBITS THE EXPRESSION OF VASOACTIVE-INTESTINAL-PEPTIDE MESSENGER-RNA IN RAT ANTERIOR-PITUITARY

Adult male Sprague-Dawley rats were treated with para-chlorophenylalanine (pCPA) or alpha-methyl tyrosine (alpha-MT) to study the effect of serotonin or catecholamine depletion on the expression of vasoactive intestinal peptide (VIP) messenger RNA in the anterior pituitary. Single injections of pCPA (300 mg/kg) for two consecutive days resulted on the third day in a dramatic depletion of serotonin in the medial basal hypothalamus, and a significant reduction in the pituitary content of VIP mRNA (1.0 and 1.7 kb). The effect of pCPA on VIP mRNA appeared to be relatively specific for the anterior pituitary since VIP message levels in the cerebral cortex did not decrease. Alpha-MT treatment, (150 mg/kg) for 2 consecutive days, reduced dopamine concentrations in the MBH but had no significant effect on pituitary VIP levels. In a time-course study, hypothalamic serotonin and pituitary VIP mRNA levels were significantly depressed 1-3 days after initiation of pCPA treatment; however, 12 days after pCPA treatment, serotonin concentrations in the hypothalamus approached control values and pituitary VIP mRNA content increased an average of 2-fold over control levels in an apparent rebound effect. pCPA-treated rats injected i.p. twice a day with 5-hydroxytryptophan (5-HTP; 50 mg/kg) experienced a partial reversal in the decline in the 1.7 kb VIP mRNA seen 24 h after the first pCPA injection. However, at 72 h, supplementation with 5-HTP did not prevent the pCPA-induced decrease of pituitary VIP mRNA. These data indicate that serotonergic pathways have a major role in the control of VIP mRNA expression in the rat anterior pituitary.