Review Reproductive neuropeptides: Prevalence of GnRH and KNDy neural signalling components in a model avian, gallus gallus Nerine T. Joseph a,⇑ , Javier A. Tello b , Gregoy Y. Bedecarrats a , Robert P. Millar c,d,e a Department of Animal and Poultry Science, University of Guelph, Guelph, Ontario, Canada b School of Medicine, University of St. Andrews, St. Andrews, United Kingdom c Mammal Research Institute, Department of Zoology and Entomology, University of Pretoria, Pretoria, South Africa d Medical Research Council Research Group for Receptor Biology, Division of Medical Biochemistry, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa e Centre for Integrative Physiology, University of Edinburgh, Edinburgh, Scotland, United Kingdom article info Article history: Available online 10 June 2013 Keywords: Avian Reproduction Neuropeptides KNDy neurone GnRH abstract Diverse external and internal environmental factors are integrated in the hypothalamus to regulate the reproductive system. This is mediated through the pulsatile secretion of GnRH into the portal system to stimulate pituitary gonadotrophin secretion, which in turn regulates gonadal function. A single sub- population of neurones termed ‘KNDy neurones’ located in the hypothalamic arcuate nucleus co-localise kisspeptin (Kiss), neurokinin B (NKB) and dynorphin (Dyn) and are responsive to negative feedback effects of sex steroids. The co-ordinated secretion from KNDy neurones appears to modulate the pulsatile release of GnRH, acting as a proximate pacemaker. This review briefly describes the neuropeptidergic control of reproduction in the avian class, highlighting the status of reproductive neuropeptide signalling systems homologous to those found in mammalian genomes. Genes encoding the GnRH system are com- plete in the chicken with similar roles to the mammalian counterparts, whereas genes encoding Kiss sig- nalling components appear missing in the avian lineage, indicating a differing set of hypothalamic signals controlling avian reproduction. Gene sequences encoding both NKB and Dyn signalling components are present in the chicken genome, but expression analysis and functional studies remain to be completed. The focus of this article is to describe the avian complement of neuropeptidergic reproductive hormones and provide insights into the putative mechanisms that regulate reproduction in birds. These postula- tions highlight differences in reproductive strategies of birds in terms of gonadal steroid feedback sys- tems, integration of metabolic signals and seasonality. Also included are propositions of KNDy neuropeptide gene silencing and plasticity in utilisation of these neuropeptides during avian evolution. Ó 2013 Elsevier Inc. All rights reserved. 1. Introduction It is well established that gonadotrophin releasing hormone (GnRH) plays a critical role in the control of reproductive function and is the ultimate signal from the brain regulating the gonadotro- phic axis in vertebrates (Millar, 2005). The pulsatile secretion of GnRH is controlled by the GnRH pulse generator, which is sensitive to environmental cues and multiple regulatory mechanisms including gonadal steroids and peptide hormones (Knobil, 1990; Krsmanovic et al., 2009; Maeda et al., 2010). Sex steroids predom- inantly feedback negatively on tonic GnRH secretion during the ovarian cycle; oestrogen inhibits GnRH pulse amplitude and pro- gesterone inhibits GnRH pulse frequency (Karsch, 1987). However, oestrogen can feedback positively on GnRH secretion at defined times of the female reproductive cycle such as during pro-oestrous where increasing oestrogen levels induce the pre-ovulatory GnRH surge (Karsch, 1987). Gonadal steroids play a central role in the to- nic and surge modes of GnRH secretion (Maeda et al., 2010; Navar- ro, 2012), but GnRH neurones lack many receptors that sense sex steroids including the oestrogen receptor alpha (ERa) and the androgen receptor (AR) Herbison and Theodosis, 1992; Huang and Harlan, 1993. For many years, it remained unclear how infor- mation regarding sex steroid milieu was transmitted to GnRH neu- rones until novel steroid responsive peptide regulators, called kisspeptins, were identified in the upstream hierarchy of hypotha- lamic neurones (de Roux et al., 2003; Pinilla et al., 2012; Seminara et al., 2003). Studies have ensued to identify the prevalence of kiss- peptin orthologues, as well as other peptides implicated to have roles in reproduction in a vast range of vertebrate genomes (sum- 0016-6480/$ - see front matter Ó 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ygcen.2013.05.018 Abbreviations: GnRH, gonadotrophin releasing hormone; Kiss, kisspeptin; NKB, neurokinin B; Dyn, dynorphin; GnIH, gonadotrophin inhibitory hormone; LH, luteinising hormone; FSH, follicle stimulation hormone; ARC, arcuate nucleus; PR, progesterone receptor; ERa, oestrogen receptor alpha; POMC, pro-opiomelanocor- tin; NPY, neuropeptide Y; MC4R, melanocortin 4 receptor. ⇑ Corresponding author. Address: Department of Animal and Poultry Science, University of Guelph, 50 Stone Road East, Building #70 Guelph, Ontario N1G 2W1, Canada. E-mail address: njoseph@uoguelph.ca (N.T. Joseph). General and Comparative Endocrinology 190 (2013) 134–143 Contents lists available at SciVerse ScienceDirect General and Comparative Endocrinology journal homepage: www.elsevier.com/locate/ygcen