Interaction between Hypothalamic Dopaminergic and Opioidergic Systems in the Photoperiodic Regulation of Pulsatile Luteinizing Hormone Secretion in Sheep

Previous studies in sheep have shown that whereas the inhibitory effects of dopamine (DA) systems on GnRH/gonadotrophin secretion are readily detectable during the sexually inactive phase under long days (LD), the suppressive effects of endogenous opioid peptide (EOP) systems are most evident during the sexually active phase under short days (SD). The hypothesis proposed in this study is that inhibitory DA pathways interact with EOP neurons to regulate GnRH/gonadotropin secretion in sheep and that photoperiod modulates this interaction to relay its effect on the seasonal reproductive cycle. To test this hypothesis, the effects of a DA agonist (bromocriptine) or of a DA antagonist (sulpiride) on the pulsatile LH response to an opioid antagonist (naloxone) were evaluated in sexually active Soay rams exposed to SD, and then reassessed when sexually inactive under LD. The experimental design comprised six treatments: 1) control (vehicle); 2) bromocriptine; 3) sulpiride; 4) naloxone; 5) pretreatment with bromocriptine followed by naloxone; 6) pretreatment with sulpiride followed by naloxone. Under SD, when DA pathways are thought to be quiescent and EOP systems active, bromocriptine suppressed pulsatile LH secretion (P < 0.01), whereas sulpiride had no effect. Under this photoperiod, naloxone induced a conspicuous stimulation of episodic LH release (P < 0.01). This effect was prevented by pretreatment with bromocriptine (P < 0.01), but was not affected by pretreatment with sulpiride. Conversely, under LD, when the activity of DA pathways is thought to be increased and that of EOP systems reduced, bromocriptine was without effect, whereas sulpiride evoked a mild increase in LH pulse frequency (P < 0.05). Under this photoperiod, naloxone induced a smaller stimulation than under SD. This effect was again blocked by pretreatment with bromocriptine but, in contrast to SD, markedly enhanced by pretreatment with sulpiride (P < 0.01). Particularly relevant was that the DA agonist blocked the stimulatory effects of the EOP antagonist under SD, and that the DA antagonist enhanced the effects of the EOP antagonist only under LD. These results are consistent with the hypothesis proposing that, in sheep, DA pathways have a predominant inhibitory effect on both GnRH and EOP neurons, and that changes in day length modulate the interplay between DA and EOP systems as part of the mechanisms involved in the photoperiodic control of the seasonal reproductive cycle.