Chronic neuropeptide Y Y5 receptor stimulation suppresses reproduction in virgin female and lactating rats.

Continuous infusion of neuropeptide Y (NPY) disrupts cyclicity and delays the onset of puberty in female rats indicating that NPY can suppress reproduction. Central application of NPY also reliably increases food intake in rats. States with heavy demands on energy resources where reproduction is also inhibited, such as lactation, are similarly accompanied by elevations in central NPY expression. In previous studies, we have shown that, compared to lactating rats fed ad libitum, food-restricted lactating rats exhibit a longer period of lactational diestrus that is correlated with increased central NPY expression. These studies link NPY to the inhibition of reproduction that is mediated by low availability of energy resources. Here, we examine the effect of chronic 7-day infusion of the mixed Y1/Y4/Y5 agonist (Leu31, Pro34) NPY and selective agonists to the Y2 (NPY13-36) and Y5 (D-Trp32 NPY and D-Trp34 NPY) receptors on food intake and the oestrous cycle of virgin female rats. We also investigated the effect of chronic infusion from day 8-15 postpartum (pp) of D-Trp32 NPY and D-Trp34 NPY on food-intake and the length of lactational diestrus in lactating rats fed ad libitum. In virgin females, infusion of (Leu31, Pro34) NPY and both the Y5 agonists lengthened the period between consecutive oestrus days while the Y2 agonist NPY13-36 was without effect. Selective Y5 receptor activation alone caused an increase in food intake in virgin females. In lactating females, D-Trp32 NPY extended the length of lactational diestrus, while D-Trp34 NPY had no effect on this parameter. These data suggest that Y5 receptor activation suppresses the reproductive axis in both virgin and lactating rats and that Y5 receptor activation enhances food-intake in virgin females.