Localization of the three GnRH types and GnRH receptors in the brain of a cichlid fish: Insights into their neuroendocrine and neuromodulator functions

Abstract

The cognate receptor for any of the known gonadotropin-releasing hormones (GnRHs) has not been directly demonstrated. In order to establish this and shed light on the functions of GnRH types, we analyzed the neuroanatomical location and time of initial expression of three distinct GnRH receptors (GnRH-Rs) and the three endogenous GnRHs in the brain of developing and sexually mature tilapia Oreochromis niloticus using immunocytochemistry. In all age groups, including males and females, GnRH-RIA was seen specifically in gonadotropes (Parhar et al. [2002] J Neuroendocrinol 14:657-665) but was undetectable in the brain. On day 8 after fertilization, GnRH-RIB was first seen in the periventricular hypothalamus (lateral recess nucleus, posterior recess nucleus, posterior tuberal nucleus) and GnRH-RIII in the olfactory epithelium, olfactory bulb, telencephalon, preoptic region, mediobasal hypothalamus, thalamus, mesencephalon, and in the hindbrain. Double-label immunocytochemistry showed GnRH1 (Ser(8) GnRH)-immunoreactive neuronal processes projecting mainly to the proximal pars distalis of the pituitary, while GnRH2 (His(5), Trp(7), Tyr(8) GnRH) and GnRH3 (Trp(7), Leu(8) GnRH) fibers were observed in close association with cells containing GnRH-RIB and GnRH-RIII in the brain. These results suggest that GnRH-RIA might be hypophysiotropic in nature, whereas GnRH-RIB and GnRH-RIII could have additional neuromodulatory functions. Further, evidence of close proximity of GnRH-R-containing cells and neuronal processes of multiple GnRH types suggests complex cross-talk between several GnRH ligands and GnRH-Rs.

Neuromodulatory Effect of GnRH on the Synaptic Transmission of the Olfactory Bulbar Neural Circuit in Goldfish, Carassius auratus

“…There are many reports showing the expression of GnRH receptors in the olfactory bulb of many vertebrates (Albertson et al 2008;Kawai et al 2009b;Maruska and Fernald 2010;Peter et al 2003;Soga et al 2005). However, few reports have described in detail their distributions in the olfactory bulb.…”

“…However, few reports have described in detail their distributions in the olfactory bulb. One of the reports suggested that one subtype of GnRH receptor is restricted to the granule cell layer in the cichlid fish olfactory bulb (Soga et al 2005), whereas another suggests that GnRHRI receptors are expressed in mitral cells of the mice olfactory bulb (Albertson et al 2008). The results of our present paired-pulse experiments strongly suggest that GnRH primarily acts on the mitral cells and presynaptically modulates their synaptic inputs to the granule cells (Manabe et al 1993;Satou et al 2006;Zucker 1989).…”

Mechanisms of Neuromodulation by a Nonhypophysiotropic GnRH System Controlling Motivation of Reproductive Behavior in the Teleost Brain

“…Thus, the peptides are supposed to diffuse for some distance to reach receptors on the neurons that are not only near the site of release but also in relatively distant locations (so-called "action at a distance" or "volume transmission" [14]). Actually, it has been reported that the GnRH receptors are not necessarily located in immediate proximity to the GnRH immunoreactive fibers in the extrahypothalamic brain regions [16][17][18]. In addition, the peptides released by such infrequent release events as described above are considered to work at very low concentrations because they have nanomolar affinity for their receptors compared with the micromolar affinity for "conventional neurotransmitters" [14].…”

“…But how does the GnRH peptide that is released from these neurons modulate the information processing of target neurons to control reproduction, especially reproductive behaviors? Recently, many researchers are interested in the forebrain olfactory and visual systems as target systems of GnRH neuromodulation because of the projection of TN-GnRH3 neurons [4,37,[42][43][44] and localization of GnRH receptors [16][17][18].…”

Seasonal Variation in the Expression of Five Subtypes of Gonadotropin-releasing Hormone Receptor Genes in the Brain of Masu Salmon from Immaturity to Spawning

“…To date, one report indicates that in cichlid fish expression of the GnRHRIII subtype is restricted to the granule cell layer (Soga et al, 2005), and another demonstrates that in mice mitral cells express GnRHRI receptors (Albertson et al, 2008). Clearly, more information concerning the regions and types of neurons that express GnRH receptors, as well as the subtypes of receptors expressed, is needed.…”