In female rats, the start of puberty depends on a rise in kisspeptin and dynorphin signals inside the brain when estrogen feedback is low and the animal has enough energy. Low estrogen cuts down kisspeptin cells before puberty, but once estrogen drops and the animal isn’t starving, kisspeptin and dynorphin go up and trigger the hormonal cascade that leads to puberty. Blocking kisspeptin in the brain delays this process, showing how crucial the kisspeptin signal is.

The pre-pubertal quiescence of pulsatile gonadotropin-releasing hormone secretion in mammals is considered due to repressed Kiss1 (encoding kisspeptin) expression in kisspeptin/neurokinin B/dynorphin A (KNDy) neurons. In this study, we aimed to investigate the effects of negative feedback levels of estradiol-17β (low E2) and energy balance on Kiss1, Tac3 (encoding neurokinin B), and Pdyn (encoding dynorphin A) expression in ovariectomized (OVX) pre- and post-pubertal rats, and the effects of central kisspeptin immunoneutralization on puberty onset in ovary-intact rats. Kiss1, Tac3, and Pdyn expression in the hypothalamic arcuate nucleus was determined using in situ hybridization or quantitative RT-PCR. Vaginal opening and first estrus were examined as indices of puberty. Low E2 markedly reduced the number of Kiss1-expressing cells in OVX pre-pubertal rats under normal diet and food-restricted conditions but had no effect in post-pubertal rats. The number of Pdyn-expressing cells was significantly lower in pre-pubertal rats than in post-pubertal rats under both dietary conditions. The numbers of Tac3-expressing cells remained elevated in all models. Furthermore, central infusion of anti-kisspeptin antibody significantly delayed puberty onset in female rats. These findings suggest that kisspeptin-dependent puberty onset in female rats is likely to be triggered by the coordinated upregulation of Kiss1 and Pdyn expression in KNDy neurons under conditions of reduced estrogen negative feedback and sufficient energy availability. In contrast, Tac3 likely plays a permissive role in puberty onset. Taken together, these results provide novel insights into how estrogen and metabolic signals converge in KNDy neurons to regulate puberty onset.