Pivotal Role of an Endogenous Tetrahydroisoquinoline, Salsolinol, in Stress- and Suckling-Induced Release of Prolactin

doi:10.1196/annals.1296.021

^aNeuroendocrine Research Laboratory, Semmelweis University, Budapest, Hungary
^bInstitute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia
^cInstitute of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Szeged, Szeged, Hungary
^dInstitute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary

In mammals, the role of a prolactin-releasing factor (PRF) inthe acute changes of prolactin (PRL) secretion that usuallyoccur after challenges (e.g., suckling stimulus or stress) ofhomeostasis has been suspected for a long time. We have recentlyobserved that 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline,salsolinol (SAL), produced by the hypothalamus and the neuro-intermediatelobe (NIL) of the pituitary gland, can selectively release PRLfrom the anterior lobe (AL). Moreover, binding sites for SALhave been detected in areas like median eminence, NIL, and AL.It has been proposed that SAL is a putative endogenous PRF.We have also found that a structural analogue of SAL, 1-methyl-3,4-dihydroisoquinoline(1MeDIQ), is able to block dose-dependently SAL-, suckling-,and immobilization (IMO) stress-induced release of PRL withouthaving any influence on ${alpha}$ -methyl-p-tyrosine ( ${alpha}$ MpT)-induced PRLresponses. Neither SAL nor 1MeDIQ has any effect on ${alpha}$ -melanocyte-stimulatinghormone ( ${alpha}$ MSH), adrenocorticotrophic hormone (ACTH), ß-endorphin(ß-END) and arginine-vasopressin (AVP) secretion.Moreover, SAL-induced PRL response was attenuated in male ratspretreated with dexamethasone (DEX). These results stronglysuggest that SAL has an important role in the regulation ofPRL release induced by physiologic and environmental stimuli;therefore, it can be considered as the strongest candidate forbeing the PRF in the hypothalamo-hypophysial system. Our findingsalso indicate that the adrenal steroids may play an inhibitoryfeedback role in SAL-mediated PRL response.