Identification of KiSS-1 Product Kisspeptin and Steroid-Sensitive Sexually Dimorphic Kisspeptin Neurons in Medaka (Oryzias latipes)

Abstract

Recently, a novel physiologically active peptide, kisspeptin (metastin), has been reported to facilitate sexual maturation and ovulation by directly stimulating GnRH neurons in several mammalian species. Despite its importance in the neuroendocrine regulation of reproduction, kisspeptin neurons have only been studied in mammals, and there has been no report on the kisspeptin or kisspeptin neuronal systems in nonmammalian vertebrates. We used medaka for the initial identification of the KiSS-1 gene and the anatomical distribution of KiSS-1 mRNA expressing neurons (KiSS-1 neurons) in the brain of nonmammalian species. In situ hybridization for the medaka KiSS-1 gene cloned here proved that two kisspeptin neuronal populations are localized in the hypothalamic nuclei, the nucleus posterioris periventricularis and the nucleus ventral tuberis (NVT). Furthermore, NVT KiSS-1 neurons were sexually dimorphic in number (male neurons >> female neurons) under the breeding conditions. We also found that the number of KiSS-1 neurons in the NVT but not that in the nucleus posterioris periventricularis was positively regulated by ovarian estrogens. The fact that there were clear differences in the number of NVT KiSS-1 neurons between the fish under the breeding and nonbreeding conditions strongly suggests that the steroid-sensitive changes in the KiSS-1 mRNA expression in the NVT occur physiologically, according to the changes in the reproductive state. From the present results, we conclude that the medaka KiSS-1 neuronal system is involved in the central regulation of reproductive functions, and, given many experimental advantages, the medaka brain may serve as a good model system to study its physiology.

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.…”

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“…Gonadal steroid levels seem to be of special importance in case of kisspeptin action on the hypothalamo-pituitary-gonadal axis in fish, since in mammals kisspeptin is responsible for the transmission of the feedback effects of sex steroids on gonadotropin release (Tena-Sempere, 2005;Smith, 2008;Roa, Aguilar, Dieguez, Pinilla, & TenaSempere, 2008;d'Anglemont de Tassigny & Colledge, 2010). Also in fish this can be true, as there are data showing that in the hypothalamus of these vertebrates the cells expressing kisspeptin co-express estrogen receptors, suggesting the role of kisspeptin in the steroid feedback on gonadotropin release (Kanda et al, 2008;Escobar et al, 2010Escobar et al, , 2013Servili et al, 2011;Cowan, Davie, & Migaud, 2012).…”

Actions of sex steroids on kisspeptin expression and other reproduction-related genes in the brain of the teleost fish european sea bass

“…The interpretation of the results in females was not so straightforward and several causes, as previously discussed, probably contributed to this situation. In medaka, only kiss1 neurons in the nucleus ventralis tuberis (NVT) are positively regulated by ovarian estrogens via their coexpressed erα (Kanda et al, 2008), while estrogen treatment of juvenile zebrafish causes an increase in kiss1 expression, although the effects on kiss2 neurons were much more pronounced (Servili et al, 2011). However, it should be noted that kiss2 expression is up-regulated by E 2 only in the POA of goldfish, showing co-localization with all three types of er genes (Kanda et al, 2012).…”

“…Little information regarding kisspeptin gene regulation is available for fish; however, it is known that kiss1 (but not kiss2) neurons are positively regulated by ovarian estrogen at the nucleus ventral tuberis (NVT) in medaka (Oryzias latipes, Temminck and Schlegel) (Kanda et al, 2008;Mitani et al, 2010). Furthermore, kiss2 neurons are sensitive to E 2 in zebrafish (Danio rerio, Hamilton) at the dorsal (Hd) and ventral (Hv) hypothalamus (Servili et al, 2011), and up-regulation of kiss2 neurons by ovarian estrogens was found to occur in the pre-optic area (POA) of goldfish (Carassius auratus, Linnaeus) (Kanda et al, 2012).…”