Serotonergic involvement in the regulation of prolactin and vasoactive intestinal peptide mRNA 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, Northeastern Ohio Universities College of Medicine, Rootstown 44272.
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Signs
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Liu
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Wolford
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Carrillo
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D001971:Bromocriptine / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006220:Haloperidol / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D008732:Methoxydimethyltryptamines / Q000494:pharmacology; D008781:Methyltyrosines / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D011388:Prolactin / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D011814:Quipazine / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000502:physiology*; D013997:Time Factors; D014158:Transcription, Genetic; D014660:Vasoactive Intestinal Peptide / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D019805:alpha-Methyltyrosine
D008732:Methoxydimethyltryptamines; D008781:Methyltyrosines; D012333:RNA, Messenger; D012701:Serotonin; D014660:Vasoactive Intestinal Peptide; D001971:Bromocriptine; D011814:Quipazine; D008719:Methiothepin; D019805:alpha-Methyltyrosine; D011388:Prolactin; D007650:Ketanserin; D006916:5-Hydroxytryptophan; D006220:Haloperidol