Molecular Biology of the Kisspeptin Receptor: Signaling, Function, and Mutations

Kisspeptin receptor (KISS1R) signaling is essential for the hallmark increase in pulsatile GnRH secretion characteristic of the onset of puberty in humans and experimental animals. Loss-of-function mutations in KISS1R are associated with idiopathic hypogonadotropic hypogonadism in humans. Also, mutations with confirmed association with idiopathic central precocious puberty were identified in kisspeptin and KISS1R. These observations underscore the role of KISS1R signaling for normal pubertal development. Moreover, investigation of the mechanisms underlying the gain-of-function mutation in KISS1R indicates that the duration of KISS1R signaling is critical for the role of this receptor in timing the onset of puberty in humans. These findings further endorse the need to uncover the mechanisms, as well as yet-unknown proteins, involved in each step of KISS1R signaling. This knowledge is expected to advance our understanding of normal and abnormal pubertal development, as well as to help uncover the role of KISS1R signaling in non-hypothalamic tissues such as the placenta. This chapter discusses recent advances in the investigation of KISS1R signaling and function, as well as potential pathophysiological implications of naturally occurring mutations in this receptor identified in humans with reproductive disorders

Genetics of vesicoureteral reflux

Primary vesicoureteral reflux (VUR) is the most common urological anomaly in children, affecting 1–2% of the pediatric population and 30–40% of children presenting with urinary tract infections (UTIs). Refluxassociated nephropathy is a major cause of childhood hypertension and chronic renal failure. The hereditary and familial nature of VUR is well recognized and several studies have reported that siblings of children with VUR have a higher incidence of reflux than the general pediatric population. Familial clustering of VUR implies that genetic factors have an important role in its pathogenesis, but no single major locus or gene for VUR has yet been identified and most researchers now acknowledge that VUR is genetically heterogeneous. Improvements in genome-scan techniques and continuously increasing knowledge of the genetic basis of VUR should help us to further understand its pathogenesis.Other funderChildren's Medical and Research Foundation6M embargo after publication - AV 8/9/2011 ke, SB-09/09/201