Organizational and activational effects of sex steroids on kisspeptin neuron development

Kisspeptin, encoded by the Kiss1 gene, is a neuropeptide required for puberty and adult reproductive function. Understanding the regulation and development of the kisspeptin system provides valuable knowledge about the physiology of puberty and adult fertility, and may provide insights into human pubertal or reproductive disorders. Recent studies, particularly in rodent models, have assessed how kisspeptin neurons develop and how hormonal and non-hormonal factors regulate this developmental process. Exposure to sex steroids (testosterone and estradiol) during critical periods of development can induce organizational (permanent) effects on kisspeptin neuron development, with respect to both sexually dimorphic and non-sexually dimorphic aspects of kisspeptin biology. In addition, sex steroids can also impart activational (temporary) effects on kisspeptin neurons and Kiss1 gene expression at various times during neonatal and peripubertal development, as they do in adulthood. Here, we discuss the current knowledge—and in some cases, lack thereof—of the influence of hormones and other factors on kisspeptin neuronal development.

► Kisspeptin, encoded by Kiss1, is a neuropeptide critical for puberty and fertility. ► Different Kiss1 populations have different phenotypes and developmental patterns. ► Sex steroids regulate kisspeptin neurons in both development and adulthood. ► Sex steroids effects on kisspeptin neurons can be organizational or activational. ► Sex steroids at birth govern sexual differentiation of select Kiss1 populations.