Endocrine Abstracts

Puberty is a key maturational process that culminates with the acquisition of reproductive capacity. This event demands significant energy resources to support the profound biological changes that occur during this period, including the activation of the reproductive axis. To this end, a plethora of signals operate for transmitting metabolic information to the reproductive axis in order to precisely regulate pubertal awakening depending on energy availability. Among others, ghrelin is an orexigenic hormone, primarily secreted by the stomach, exerting its effect via activation of the growth hormone secretagogue receptor (GHS-R1a), with crucial implications in the control of metabolism and puberty onset. In recent years, special attention has been also paid to the hepatic peptide LEAP-2, identified as a potential antagonist of ghrelin receptor, particularly in the context of energy homeostasis. However, the influence of LEAP-2 on pubertal maturation has not yet been explored. Therefore, the aim of this project was to unveil the contribution of LEAP-2 to the metabolic control of puberty. To this regard, we investigated the impact of LEAP-2 treatment during the pubertal transition in intact female Wistar rats under different metabolic conditions. In addition, we analyzed the effect of chronic administration of LEAP-2 to ovariectomized peripubertal rats replaced with physiological levels of estradiol (OVX+E2) to avoid the potential confounding effects of fluctuating sex steroid levels. Our results revealed that acute central administration of LEAP-2 increases luteinizing hormone (LH) release in a dose-dependent manner in peripubertal rats subjected to 24 h fasting, an experimental condition known to elevate circulating ghrelin levels. In the same line, chronic central administration of LEAP-2 to prepubertal female rats, either fed ad libitum (normonutrition) or subjected to 20% food restriction, induced a significant advance in puberty onset. This effect was defined by earlier vaginal opening, increased LH levels and accelerated ovarian maturation, regardless the nutritional status of the animals, being this effect more pronounced in undernourished animals. Similar effect on LH levels was detected in OVX+E2 animals treated with LEAP-2. Notably, central treatment with LEAP-2 in OVX+E2 rats led to an increase in Kiss1 mRNA levels, smggesting a potential implication of this neuropeptide in the actions of LEAP-2 on puberty onset under different metabolic conditions. Altogether, our data provide the first evidence about the important role of LEAP-2 in the metabolic control of pubertal maturation, potentially via Kiss1 neurons.