Differential and Gonad Stage-Dependent Roles of Kisspeptin1 and Kisspeptin2 in Reproduction in the Modern Teleosts, Morone Species1

Abstract

Kisspeptin is an important regulator of reproduction in many vertebrates. The involvement of the two kisspeptins, Kiss1 and Kiss2, and their receptors, Gpr54-1 and Gpr54-2, in controlling reproduction was studied in the brains of the modern teleosts, striped and hybrid basses. In situ hybridization and laser capture microdissection followed by quantitative RT (QRT)-PCR detected coexpression of kiss1 and kiss2 in the hypothalamic nucleus of the lateral recess. Neurons expressing gpr54-1 and gpr54-2 were detected in several brain regions. In the preoptic area, gpr54-2 was colocalized in GnRH1 neurons while gpr54-1 was expressed in cells attached to GnRH1 fibers, indicating two different modes of GnRH1 regulation. The expression of all four genes was measured in the brains of males and females at different life stages using QRT-PCR. The levels of kiss1 and gpr54-1 mRNA, the latter being expressed in minute levels, were consistently lower than those of kiss2 and gpr54-2. While neither gene's expression increased at prepuberty, all were dramatically elevated in mature females. The levels of kiss2 mRNA increased also in mature males. Kiss1 peptide was less potent than Kiss2 in elevating plasma luteinizing hormone levels and in up-regulating gnrh1 and gpr54-2 expression in prepubertal hybrid bass in vivo. In contrast, during recrudescence, Kiss1 was more potent than Kiss2 in inducing luteinizing hormone release, and Kiss2 down-regulated gnrh1 and gpr54-2 expression. This is the first report in fish to demonstrate the alternating actions and the importance of both neuropeptides for reproduction. The organization of the kisspeptin system suggests a transitional evolutionary state between early to late evolving vertebrates.

MOLECULAR EVOLUTION OF GPCRS: Kisspeptin/kisspeptin receptors

“…Only the Kiss2 gene is present in some species such as fugu (Takifugu niphobles), tetraodon (Tetraodon nigroviridis), and stickleback (Gasterosteus aculeatus) (Pasquier et al 2012b). In contrast, the Kiss1 and Kiss2 genes have been characterized in some other species including zebrafish (Danio rerio) (Biran et al 2008), goldfish (Carassius auratus) (Li et al 2009), medaka (Oryzias latipes) (Lee et al 2009b), chub mackerel (Scomber japonicus) (Selvaraj et al 2010), striped bass (Morone saxatilis) (Zmora et al 2012), and European eel (Pasquier et al 2012b).…”

“…All teleost species investigated so far express the KissR2 gene . However, some species also possess the KissR3 gene, including zebrafish (D. rerio) (Biran et al 2008), goldfish (C. auratus) (Li et al 2009), medaka (O. latipes) (Lee et al 2009b), striped bass (M. saxatilis) (Zmora et al 2012), chub mackerel (S. japonicus) (Ohga et al 2013), and European eel (Anguilla anguilla) (Pasquier et al 2012a). In addition, the eel presents the peculiarity of being the only teleost species possessing a kissR1 gene orthologous to the mammalian KissR1.…”

Effects of growth hormone over-expression on reproduction in the common carp Cyprinus carpio L.

“…While the robust stimulatory effects of GnRH on LH production are well established in teleost as in other vertebrates, the role of the kisspeptins is poorly understood. There is evidence for stimulatory effects of kisspeptin on LH transcription and secretion (Felip et al, 2009;Kitahashi et al, 2009;Li et al, 2009;Zmora et al, 2012). However, kisspeptin is an inhibitor of LH expression in eel (Anguilla anguilla) (Pasquier et al, 2011).…”

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.…”