Molecular Biology of the Kisspeptin Receptor: Signaling, Function, and Mutations - Kisspeptin Signaling in Reproductive Biology - page 129

Chapter 7
Molecular Biology of the Kisspeptin Receptor:
Signaling, Function, and Mutations
Suzy Drummond Carvalho Bianco and Ursula B. Kaiser
Abstract 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
confi rmed association with idiopathic central precocious puberty were identifi ed in
kisspeptin and KISS1R. These observations underscore the role of KISS1R signal-
ing 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 fi ndings 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 puber-
tal 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 pathophysi-
ological implications of naturally occurring mutations in this receptor identifi ed in
humans with reproductive disorders.
S. D. C. Bianco
Department of Molecular and Cellular Pharmacology and Department of Medicine,
University of Miami Miller School of Medicine , Miami , FL , USA
e-mail: [e-mail]
U. B. Kaiser , M.D. ( * )
Division of Endocrinology, Department of Medicine, Harvard Medical School/Brigham
and Women's Hospital, 221 Longwood Avenue , Boston , MA 02115 , USA
e-mail: [e-mail]