Kisspeptin and Clinical Disorders - Kisspeptin Signaling in Reproductive Biology - page 183

Chapter 9
Kisspeptin and Clinical Disorders
Letícia Gontijo Silveira , Ana Claudia Latronico ,
and Stephanie Beth Seminara
Abstract The hypothalamic hormone GnRH has traditionally been viewed as a central
driver of the hypothalamic-pituitary-gonadal axis. Pulsatile GnRH release is required for
pulsatile gonadotropin secretion, which then modulates gonadal steroid feedback and
brings about full fertility in the adult. Pathways governing GnRH ontogeny and physiol-
ogy have been discovered by studying humans with disorders of GnRH secretion. In this
chapter, the human genetics of the kisspeptin signaling pathway in patients with diverse
reproductive phenotypes will be explored. The discovery of defects in the kisspeptin
system in several reproductive disorders has shed light on the mechanisms involved in
regulating GnRH secretion, revealing the critical role played by the kisspeptin signaling
pathway in pubertal initiation and reproductive function.
GnRH Defi ciency
GnRH defi ciency is a condition characterized by abnormal pubertal development
and low gonadotropins and sex steroids. Administration of exogenous pulsatile
GnRH long term can restore normal levels of gonadotropins and sex steroids in
patients with this disorder, demonstrating the hypothalamic nature of the defect in
the vast majority of patients [ 1 , 2 ]. GnRH defi ciency is heterogenous in its clinical
L. G. Silveira • A. C. Latronico
Department of Internal Medicine, Division of Endocrinology and Metabolism,
Hospital das Clinicas, Sao Paulo University, Sao Paulo, Brazil
e-mail: [e-mail]
S. B. Seminara , M.D. ( * )
Department of Internal Medicine, Reproductive Endocrine Unit,
Bartlett Hall Extension 504, Endocrine Division, Massachusetts General Hospital,
55 Fruit Street , Boston , MA 02114 , USA
e-mail: [e-mail]