Kisspeptin signaling in the brain: Recent developments and future challenges

Abstract

Kisspeptins, a family of peptides encoded by the KISS1 gene which binds GPR54 (or KISS1 receptor), have recently emerged as essential neuropeptide regulators of key aspects of reproductive maturation and function, including puberty onset, neuroendocrine control of ovulation and metabolic regulation of fertility. Yet, while the neuroanatomy of kisspeptin system has begun to be deciphered, and the involvement of kisspeptins in the above phenomena has been experimentally documented in recent years, precise information on the signaling events underlying these functions has remained scarce. Similarly, the nature and mechanisms of action of most of the regulatory signals of KISS1 expression in the brain are largely unknown. In this review, we will comprehensively summarize some of the recent developments in these areas of kisspeptin physiology, with the ultimate aim to delineate unresolved questions and future pathways for the progression of this active field of Neuroendocrinology.

Differential activation of kiss receptors by Kiss1 and Kiss2 peptides in the sea bass

“…Accumulating evidence has provided insight into the involvement of the kisspeptin system in the regulation of neuronal systems other than those involved in vertebrate reproduction, such as those related to complex behaviors, including sexual motivation and arousal states (Parhar et al 2004, Kanda et al 2008, Tena-Sempere 2010a, Servili et al 2011, Shimizu et al 2012, Zhao & Wayne 2012, Zmora et al 2012, Escobar et al 2013a. Expression levels of kiss and kissr in the brain and, to a lesser extent, in the gonad have been analyzed in several non-mammalian species, including amphibians (Chianese et al 2013) and fish (Mohamed et al 2007, Nocillado et al 2007, Biran et al 2008, Filby et al 2008, van Aerle et al 2008, Kitahashi et al 2009, Mechaly et al 2009, Migaud et al 2012, Alvarado et al 2013, Ohga et al 2013, suggesting a putative role for kisspeptins in controlling reproduction.…”

Intraperitoneal kisspeptin-10 administration induces dose-dependent degenerative changes in maturing rat testes

“…These studies collectively point out that kisspeptins are likely to be the most potent elicitors of GnRH/gonadotropin secretion (Roa et al, 2008;Tena-Sempere, 2010) however, little is known about the effects of kisspeptin on testicular tissue and the process of spermatogenesis. Thompson et al (2006Thompson et al ( , 2009 showed that chronic administration of kisspeptin to adult rats causes testicular degeneration, an effect that can be prevented by pretreatment with cetrorelix, a GnRH antagonist.…”

Endocannabinoids and Kisspeptins: Two Modulators in Fight for the Regulation of GnRH Activity

“…Conditions of hypoleptinemia have been linked to decreased hypothalamic expression of kiss1 mRNA and to the inhibition of reproductive functions (Smith et al, 2006). Since GnRH neurons do not directly respond to nutritional conditions (Louis et al, 2011), current hypothesis is that kisspeptin neurons represent intermediate obligate pathways to transmit leptin actions to GnRH neurons that do not express leptin receptor , Smith et al, 2006, Tena-Sempere, 2010). …”