Neurokinin Bs and neurokinin B receptors in zebrafish-potential role in controlling fish reproduction

Abstract

The endocrine regulation of vertebrate reproduction is achieved by the coordinated actions of several peptide neurohormones, tachykinin among them. To study the evolutionary conservation and physiological functions of neurokinin B (NKB), we identified tachykinin (tac) and tac receptor (NKBR) genes from many fish species, and cloned two cDNA forms from zebrafish. Phylogenetic analysis showed that piscine Tac3s and mammalian neurokinin genes arise from one lineage. High identity was found among different fish species in the region encoding the NKB; all shared the common Cterminal sequence. Although the piscine Tac3 gene encodes for two putative tachykinin peptides, the mammalian ortholog encodes for only one. The second fish putative peptide, referred to as neurokinin F (NKF), is unique and found to be conserved among the fish species when tested in silico. tac3a was expressed asymmetrically in the habenula of embryos, whereas in adults zebrafish tac3a-expressing neurons were localized in specific brain nuclei that are known to be involved in reproduction. Zebrafish tac3a mRNA levels gradually increased during the first few weeks of life and peaked at pubescence. Estrogen treatment of prepubertal fish elicited increases in tac3a, kiss1, kiss2, and kiss1ra expression. The synthetic zebrafish peptides (NKBa, NKBb, and NKF) activated Tac3 receptors via both PKC/Ca 2+ and PKA/cAMP signal-transduction pathways in vitro. Moreover, a single intraperitoneal injection of NKBa and NKF significantly increased leuteinizing hormone levels in mature female zebrafish. These results suggest that the NKB/NKBR system may participate in neuroendocrine control of fish reproduction.gonadotropin-releasing hormone | kisspeptin | teleost | gonadotropin R eproduction is a highly integrated and complex function that requires synchronized production of gametes by both sexes at an optimum time for offspring survival. Fish show an enormous variety of reproductive strategies (1), and were recently chosen as models for the study of growth, metabolism, and human diseases. The hypothalamic regulation of gonadotropin secretion in fish is different from that of mammals, from both endocrinal and anatomical aspects. In teleosts, the pituitary is innervated directly by neurons projecting to the vicinity of the pituitary gonadotrophs (2). Among the neuropeptides released by these nerve endings are gonadotrophin-releasing hormones (GnRHs) and dopamine, which act as stimulatory and inhibitory factors on the release of luteinizing hormone (LH) and follicle-stimulating hormone (3). However, new actors have recently entered the field of reproductive physiology: kisspeptins, neurokinin, and dynorphin have all been implicated in controlling GnRH (4).Topaloglu et al. (5) found that humans bearing loss-of-function mutations of the genes encoding either neurokinin B (NKB) or its cognate receptor, neurokinin receptor 3 (NKBR, Tac3r) displayed hypogonadotropic hypogonadism; this seminal report implicated NKB signaling as an essential factor in the onset of puberty...

Acute anorexigenic action of leptin in rainbow trout is mediated by the hypothalamic Pi3k pathway

“…These data are also in agreement with data on frog Xenopus laevis, where ICV Lep administration increases pomc transcription (Cui et al 2014). Also in mammals, LEP primarily acts on the POMC/CART neurons in the ARC (Varela & Horvath 2012), while in fish, the NLT of the hypothalamus is considered to be homologous to the mammalian ARC (Biran et al 2012). Collectively, these studies support the notion that the role of Lep in regulating Pomc neurons in the mediobasal hypothalamus has been conserved through vertebrate evolution.…”

“…In the ARC, LEP inhibits the gene expression of the orexigenic neuropeptide Y (NPY) and agouti-related peptide (AGRP), and stimulates the expression of the anorexigenic proopiomelanocortin (POMC) and cocaine-and amphetamine-regulated transcript (CART) (Kristensen et al 1998, Bates et al 2003, Morrison et al 2005. The piscine structure homologous to mammalian ARC is the nucleus lateralis tuberis (NLT) within the tuberal hypothalamic region (Berman et al 2009, Biran et al 2012. The lateral tuberal hypothalamus is involved in neuroendocrine regulation of the pituitary gland, particularly within the more caudally located NLT region, the periventricular zone along the infundibulum (INF), and lateral recess that is surrounded by the nucleus anterior tuberis (NAT) located rostral to the infundibulum (Meek & Nieuwenhuys 1998).…”

Tachykinin: recent developments and novel roles in health and disease

“…NPK and NPγ are forms of NKA with N-terminal extensions of 26 and 11 amino acids residues, respectively (3,5). NKB and neuropeptide F (NKF) are encoded in the Tac3 (pre-pro-tachykinin B, Ppt-b, or Tac2 in rodents) gene (7,8), while HK-1 and EKs are encoded by the Tac4 (pre-pro-tachykinin C, Ppt-c) gene (6,9,10). Tac4 encodes HK-1 in the mouse and rat, whereas Tac4 is spliced into four variants (α to δ) in humans to produce EK-A to EK-D, respectively (10).…”

Neprilysins: An Evolutionarily Conserved Family of Metalloproteases That Play Important Roles in Reproduction in Drosophila

“…In the sea squirt, Ciona intestinalis, tachykinins regulate oocyte growth (Aoyama et al 2012). Between mammals and the zebrafish, Danio rerio, the estrogendependent features of tachykinins and their receptors appear to be conserved (Biran et al 2012). In the insects Drosophila melanogaster and Tribolium castaneum, the tachykinin-like neuropeptide, natalisin, plays a role in regulating mating and reproductive outcomes (Jiang et al 2013).…”