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 con trol of prolactin (PRL) and vasoactive intestinal peptide (VIP) messen ger RNA expression in rat anterior pituitary. Daily injection of rats with the biosynthetic precursor to serotonin, 5-hydroxytryptophan (5-H TP; 25 mg/kg, q.i.d.), resulted on day 5 in a 50% increase in the expr ession of PRL mRNA in the pituitary while at the same time reducing th e 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, alp ha-methyl-tyrosine (alpha-MT; 150 mg/kg, q.d. X 2 days), or the dopami ne receptor antagonist haloperidol (1.25 mg/kg, b.i.d. X 5 days), resu lted in increases in pituitary PRL message levels that were greater th an those observed with either anti-dopaminergic agent alone. In contra st, 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 bromocr iptine had a significant effect on pituitary VIP mRNA expression. Admi nistration of the direct-acting 5-HT receptor agonist quipazine (5 mg/ kg, b.i.d.) for 14 consecutive days caused a significant increase in p ituitary PRL mRNA levels on day 1 and reached a plateau of 90% above c ontrol 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 rece ptor blocker ketanserin (8 mg/kg t.i.d. X 3 days) were unable to atten uate pituitary PRL mRNA levels. The presynaptic 5-HT autoreceptor agon ist 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 pituitar y PRL and VIP mRNA expression.