Does melatonin act on dopaminergic pathways in the mediobasal hypothalamus to mediate effects of photoperiod on prolactin secretion in the ram?
Previous studies have shown that the chronic administration of melatonin in the mediobasal hypothalamus (MBH) using micro-implants in Soay rams housed under long days causes a sustained decrease in the secretion of prolactin as occurs in response to short days. The purpose of this study was to investigate whether hypothalamic dopaminergic (DA) systems acting through D2 receptors may be involved in this melatonin-induced effect. Groups of Soay rams living under long days were treated in the MBH with micro-implants containing bromocriptine (BROM, DA D2 receptor agonist), or sulpiride (SULP, DA D2 receptor antagonist), given alone or in combination with melatonin (MEL), to establish whether the DA drugs would mimic or negate the effects of melatonin. A control group (C) received empty micro-implants or no treatment. The micro-implants were bilateral and were left in place for 14 weeks; the trial continued for a total of 28 weeks (14-week implant period and 14-week post-implant period) while the animals remained under long days. The ability of the micro-implants to release BROM and SULP for 14 weeks was confirmed by incubating implants in vitro and testing for the presence of the compounds using a pituitary cell bioassay. MEL in the MBH induced a marked decrease in the blood plasma concentrations of prolactin during the implant period and an increase during the postimplant period (MEL vs. C, p < 0.001). BROM given alone induced a sustained decrease in the plasma concentrations of prolactin (less marked than MEL), while SULP caused an increase (BROM and SULP vs. C, p < 0.001); the effects were restricted to the implant period. BROM given in combination with MEL produced the same effect as MEL alone during both the implant and postimplant periods, while SULP given with MEL produced the same effect as MEL during the implant period, but impaired the increase in plasma concentrations of prolactin during the postimplant period (MEL + SULP vs. MEL, p < 0.001). There were changes in growth and moulting of the pelage correlated with the marked changes in the secretion of prolactin induced by MEL, but not related to the lesser effects of BROM and SULP. In conclusion, the long-term effects of the D2 agonist and antagonist are consistent with the inhibitory role of hypothalamic DA pathways in the homeostatic regulation of prolactin secretion. The inhibitory effect of the D2 agonist did not mimic that of MEL in the MBH, thus it is unlikely that the short day MEL signal operates primarily through a hypothalamic DA system to inhibit the secretion of prolactin. However, since the administration of the D2 antagonist in the MBH did influence the response to MEL, it is probable that DA pathways are involved in relaying the effects of MEL on the long-term cycle in the secretion of prolactin in the ram.
Lincoln
G A
GA
MRC Reproductive Biology Unit, Centre for Reproductive Biology, Edinburgh, UK.
Tortonese
D J
DJ
D000704:Analysis of Variance; D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects*; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects*; D008550:Melatonin / Q000494:pharmacology*; D009434:Neural Pathways / Q000187:drug effects*; D017440:Photoperiod; D010902:Pituitary Gland / Q000378:metabolism; D011388:Prolactin / Q000097:blood / Q000378:metabolism*; D012756:Sheep; D013997:Time Factors
D011388:Prolactin; D008550:Melatonin; D004298:Dopamine