Hypothalamic neurotransmitter function in experimentally induced hyperprolactinemia.
It is known that animals or patients bearing a prolactin (PRL)-secreting tumor (PST) do not suppress PRL levels after administration of indirectly acting dopamine agonists, namely nomifensine (Nom), and are not responsive to the PRL releasing effect of antidopaminergic drugs and opioid peptides. Since the action of these drugs is mediated through the tuberoinfundibular dopaminergic (TIDA) system, these findings have been taken to indicate that animals and humans bearing prolactinomas have a defective TIDA function. Alternatively, PRL unresponsiveness to these drugs could be due to hyperfunction of TIDA system for the feedback action of high PRL levels. To clarify whether hypo- or hyperfunction of the TIDA system was responsible for such behaviour, we tested the effect of a synthetic opioid peptide (FK 33-824), a DA receptor antagonist, domperidone (Dom), and of Nom on PRL secretion in two experimental models of non-tumoral hyperprolactinemia, i.e. rats bearing ectopic pituitaries since 3 days (TP rats), or treated with ovine PRL (oPRL 250 micrograms, twice daily for 3 days), in which existence of an increased TIDA function has been demonstrated. FK 33-824 (0.5 mg/kg i.p.) increased significantly plasma PRL levels in control rats but failed to do so in TP rats and it elicited a significantly lower PRL response than in controls in rats treated with oPRL. In both experimental models, a PRL secretagogue, e.g. 5-hydroxytryptophan (50 mg/kg i.p.), elicited the same response as in controls, indicating that the pituitary PRL pool was preserved.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin / Q000494:pharmacology; D004294:Domperidone / Q000494:pharmacology; D004298:Dopamine / Q000032:analysis / Q000502:physiology*; D005260:Female; D007031:Hypothalamus / Q000502:physiology*; D008473:Median Eminence / Q000032:analysis; D009270:Naloxone / Q000494:pharmacology; D009627:Nomifensine / Q000494:pharmacology; D011388:Prolactin / Q000097:blood*; D051381:Rats; D011919:Rats, Inbred Strains; D009435:Synaptic Transmission
D009627:Nomifensine; D009270:Naloxone; D004294:Domperidone; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; D011388:Prolactin; D004298:Dopamine