Pubertal immune challenge suppresses the hypothalamic-pituitary-gonadal axis in male and female mice

Abstract

Kisspeptin is a neuropeptide responsible for propagating the hypothalamic-pituitary-gonadal (HPG) axis and initiating puberty. Pubertal exposure to an immune challenge causes enduring sexual behavior dysfunction in males and females, but the mechanism underlying this stress-induced sexual dysfunction remains unknown. Previous findings show that stress exposure can downregulate the HPG axis in adult females. However, it is unclear whether stress induced HPG axis suppression is limited to adult females or also extends to males and to pubertal animal models. The current study was designed to investigate the sex-specific consequences of a pubertal immune challenge on specific components of the HPG axis. Six-week old pubertal male and female mice were treated with saline or with lipopolysaccharide, a bacterial endotoxin. Expression of hypothalamic Kiss1 and Kiss1R as well as serum concentrations of luteinizing hormone, follicle-stimulating hormone, and growth hormone were examined. Pubertal lipopolysaccharide treatment decreased hypothalamic Kiss1, but not Kiss1R, expression in both males and females. Furthermore, only males showed decreases in circulating luteinizing and follicle-stimulating hormones. These results show that pubertal immune challenge suppresses the HPG axis by inhibiting Kiss1 production and decreasing serum gonadotropin concentrations in pubertal males, but points to a different mechanism in pubertal females.

Keywords: Hormones; Kisspeptin; Lipopolysaccharide; Puberty; Sex differences; Stress.