Abstract
Neurons co-synthesizing kisspeptin (KP), neurokinin B (NKB), and dynorphin (“KNDy neurons”) in the hypothalamic arcuate/infundibular nucleus (INF) form a crucial component of the gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) “pulse generator.” The goal of our study was to characterize KP neuron distribution, neuropeptide phenotype and connectivity to GnRH cells in ovariectomized (OVX) dogs and cats with immunohistochemistry on formalin-fixed hypothalamic tissue sections. In both species, KP and NKB neurons occurred in the INF and the two cell populations overlapped substantially. Dynorphin was detected in large subsets of canine KP (56%) and NKB (37%) cells and feline KP (64%) and NKB (57%) cells; triple-labeled (“KNDy”) somata formed ∼25% of all immunolabeled neurons. Substance P (SP) was present in 20% of KP and 29% of NKB neurons in OVX cats but not dogs, although 26% of KP and 24% of NKB neurons in a gonadally intact male dog also contained SP signal. Only in cats, cocaine- and amphetamine regulated transcript was also colocalized with KP (23%) and NKB (7%). In contrast with reports from mice, KP neurons did not express galanin in either carnivore. KP neurons innervated virtually all GnRH neurons in both species. Results of this anatomical study on OVX animals reveal species-specific features of canine and feline mediobasal hypothalamic KP neurons. Anatomical and neurochemical similarities to and differences from the homologous KP cells of more extensively studied rodent, domestic and primate species will enhance our understanding of obligate and facultative players in the molecular mechanisms underlying pulsatile GnRH/LH secretion.
Highlights
Pulsatile secretion of hypothalamic gonadotropin-releasing hormone (GnRH) and adenohypophysial luteinizing hormone (LH) is crucial for mammalian fertility (Belchetz et al, 1978; Santoro et al, 1986)
Evidence accumulated over the past two decades indicates that two populations of kisspeptin (KP) synthesizing neurons located in the preoptic region and in the arcuate (ARC)/infundibular (INF) nucleus of the mediobasal hypothalamus, respectively, are key regulators of GnRH/LH secretion
Axo-axonal Communication Between Kisspeptin and GnRH Neurons in the Median Eminence The distribution of hypophysiotropic GnRH fibers in the median eminence (ME) overlapped with a dense KP-IR fiber plexus in both dogs and cats (Figures 3B,D)
Summary
Pulsatile secretion of hypothalamic gonadotropin-releasing hormone (GnRH) and adenohypophysial luteinizing hormone (LH) is crucial for mammalian fertility (Belchetz et al, 1978; Santoro et al, 1986). Kisspeptin stimulates LH release (Gottsch et al, 2004; Dhillo et al, 2005; Messager et al, 2005; Plant et al, 2006; AlbersWolthers et al, 2014, 2016) via directly activating GnRH neurons, which express the KP receptor (Kiss1r) (Irwig et al, 2004; Han et al, 2005; Messager et al, 2005) This mechanism is so basic for reproduction that ablation of Kiss1r from GnRH neurons causes infertility, and fertility can be reinstated to mice bearing global Kiss1r deletion via the selective reinsertion of the Kiss1r into GnRH neurons (Kirilov et al, 2013). Excitatory NKB neurotransmission via NK3 autoreceptors and inhibitory Dyn signaling via κ-opioid autoreceptors play crucial roles in this communication (Navarro et al, 2011; de Croft et al, 2013; Ruka et al, 2013; Qiu et al, 2016)
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