SEROTONERGIC INVOLVEMENT IN THE REGULATION OF PROLACTIN AND VASOACTIVE-INTESTINAL-PEPTIDE MESSENGER-RNA EXPRESSION IN THE RAT ANTERIOR-PITUITARY

These studies examined the contribution of serotonin (5-HT) to the control of prolactin (PRL) and vasoactive intestinal peptide (VIP) messenger RNA expression in rat anterior pituitary. Daily injection of rats with the biosynthetic precursor to serotonin, 5-hydroxytryptophan (5-HTP; 25 mg/kg, q.i.d.), resulted on day 5 in a 50% increase in the expression of PRL mRNA in the pituitary while at the same time reducing the levels of both the 1.0 and 1.7 kb VIP mRNA transcripts. Co-treatment of rats with 5-HTP plus the catecholamine biosynthesis inhibitor, alpha-methyl-tyrosine (alpha-MT; 150 mg/kg, q.d. X 2 days), or the dopamine receptor antagonist haloperidol (1.25 mg/kg, b.i.d. X 5 days), resulted in increases in pituitary PRL message levels that were greater than those observed with either anti-dopaminergic agent alone. In contrast, 5-HTP was unable to reverse the inhibition of PRL mRNA expression caused by treatment with the dopamine receptor agonist bromocriptine (2.5 mg/kg, b.i.d. X 5 days). Neither alpha-MT, haloperidol nor bromocriptine had a significant effect on pituitary VIP mRNA expression. Administration of the direct-acting 5-HT receptor agonist quipazine (5 mg/kg, b.i.d.) for 14 consecutive days caused a significant increase in pituitary PRL mRNA levels on day 1 and reached a plateau of 90% above control levels on days 7 and 14. VIP mRNA levels rose significantly on day 1 of quipazine treatment but thereafter fell to a minimum of 22% (1.0 kb) and 52% (1.7 kb) of control by day 14. Both the 5-HT1 receptor antagonist methiothepin (1 mg/kg, t.i.d. X 3 days) and the 5-HT2 receptor blocker ketanserin (8 mg/kg t.i.d. X 3 days) were unable to attenuate pituitary PRL mRNA levels. The presynaptic 5-HT autoreceptor agonist 5-MeODMT (6 mg/kg, t.i.d. X 3 days) was equally ineffective. Each of these drugs, however, was able to produce marked reductions in VIP mRNA content in the anterior pituitary. This study indicates that the serotonergic system contributes to the regulation of anterior pituitary PRL and VIP mRNA expression.