Interactions Between Kisspeptins and Neurokinin B - Kisspeptin Signaling in Reproductive Biology - page 316

Chapter 15
Interactions Between Kisspeptins
and Neurokinin B
Víctor M. Navarro
Abstract Reproductive function is tightly regulated by an intricate network of
central and peripheral factors; however, the precise mechanism triggering critical
reproductive events, such as puberty onset, remains largely unknown. Recently, the
neuropeptides kisspeptin (encoded by Kiss1 ) and neurokinin B (NKB, encoded by
TAC3 in humans and Tac2 in rodents) have been placed as essential gatekeepers of
puberty. Studies in humans and rodents have revealed that loss-of-function muta-
tions in the genes encoding either kisspeptin and NKB or their receptors, Kiss1r and
neurokinin 3 receptor (NK3R), lead to impaired sexual maturation and infertility.
Kisspeptin, NKB, and dynorphin A are co-expressed in neurons of the arcuate
nucleus (ARC), so-called K isspeptin/ N KB/ Dy n (KNDy) neurons. Importantly, these
neurons also co-express NK3R. Compelling evidence suggests a stimulatory role of
NKB (or the NK3R agonist, senktide) on LH release in a number of species. This
effect is likely mediated by autosynaptic inputs of NKB on KNDy neurons to induce
the secretion of gonadotropin-releasing hormone (GnRH) in a kisspeptin-dependent
manner, with the coordinated actions of other neuroendocrine factors, such as dyn-
orphin, glutamate, or GABA. Thus, we have proposed a model in which NKB feeds
back to the KNDy neuron to shape the pulsatile release of kisspeptin, and hence
GnRH, in a mechanism also dependent on the sex steroid level. Additionally, NKB
may contribute to the regulation of the reproductive function by metabolic cues.
Investigating how NKB and kisspeptin interact to regulate the gonadotropic axis
will offer new insights into the control of GnRH release during puberty onset and
the maintenance of the reproductive function in adulthood, offering a platform for
the understanding and treatment of a number of reproductive disorders.
V. M. Navarro , Ph.D. ( * )
Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital
and Harvard Medical School, Boston , MA 02115 , USA
e-mail: [e-mail]