Leptin/leptinR-kisspeptin/kiss1r-GnRH pathway reacting to regulate puberty onset during negative energy balance

Abstract

Aims: Reproductive endocrine disorder induced by negative energy balance is very common in recent years. But underlying mechanism of reproductive disorders still remains elusive. It is reported that leptin/leptinR-kisspeptin/kiss1r system plays a critical role in reproductive field. Therefore, this study was to determine the role of leptin/leptinR in the expression of kisspeptin/kiss1r during negative energy balance and effect of leptin/leptinR-kisspeptin/kiss1r on puberty onset.

Materials and methods: Wistar female rats aged 28days were divided into four groups. The saline and leptin treatment groups were treated through intracerebroventricular injection while 72h-fasting. Body weight and serum hormone levels were recorded. The levels of mRNA and protein of kisspeptin, kiss1r, GnRH and leptinR were measured by QT-PCR, Immunofluorescence and Western blot, respectively.

Key findings: Kisspeptin, kiss1r and GnRH expression was detected in the cytoplasm but leptinR in the nucleus. After fasting, the results show a significant decrease in body weight, serum levels of leptin, LH and FSH concentrations and the expression of kisspeptin/kiss1r, GnRH mRNA and reproductive endocrine peptides. Leptin administration had no effects on body weight but it was found that the serum levels of leptin, LH and FSH were increased. Leptin shows slight effects on inhibiting the suppression of fasting. The leptinR expression of ARC increased after fasting and was restricted by leptin injection.

Significance: Leptin/leptinR-kisspeptin/kiss1r-GnRH pathway is responsible for the regulation of neuroendocrine hormones due to its effect on the protein or mRNA expression. Subsequently, it affects the reproductive function, especially could delay puberty onset.

Keywords: Estradiol (PubChem CID: 5757); Fasting; Gonadotropin -releasing hormone (PubChem CID: 44354963); Gonadotropin-releasing hormone; Kisspeptin (PubChem CID: 90488921); Kisspeptins; Leptin; Leptin (PubChem CID: 90470904); Puberty.