Role of Kisspeptin and NKB in Puberty in Nonhuman Primates: Sex Differences

To understand the roles of kisspeptin and neurokinin B (NKB) in puberty and sex differences in their involvement, we conducted a series of experiments measuring the release of gonadotropin-releasing hormone (GnRH) and kisspeptin in the median eminence of the hypothalamus in male and female monkeys throughout sexual development. Results indicate that kisspeptin-10 and the NKB agonist, senktide, stimulated GnRH release in males and females at the prepubertal and pubertal stages, but females are much more sensitive to kisspeptin signaling than males. Moreover, throughout the progress of puberty, major remodeling of kisspeptin and NKB signaling pathways for the regulation of GnRH release takes place. In females during puberty, reciprocal pathways (i.e., kisspeptin signaling mediated through NKB neurons and NKB signaling mediated through kisspeptin neurons) are established, to provide powerful and flexible mechanisms for GnRH neurosecretory activity necessary for complex female reproductive function in adulthood. By contrast, during puberty in males, reciprocal pathways are consolidated to a simpler kisspeptin-dominant signaling pathway. Nevertheless, in primates, both kisspeptin and NKB signaling are contributing factors for the pubertal increase in GnRH release, rather than initiating puberty.