Multiple functions of non-hypophysiotropic gonadotropin releasing hormone neurons in vertebrates

Abstract

Gonadotropin releasing hormone (GnRH) is a hypophysiotropic hormone that is generally thought to be important for reproduction. This hormone is produced by hypothalamic GnRH neurons and stimulates the secretion of gonadotropins. On the other hand, vertebrates also have non-hypophysiotropic GnRH peptides, which are produced by extrahypothalamic GnRH neurons. They are mainly located in the terminal nerve, midbrain tegmentum, trigeminal nerve, and spinal cord (sympathetic preganglionic nerves). In vertebrates, there are typically three gnrh paralogues ( gnrh1 , gnrh2 , gnrh3 ). GnRH-expression in the non-hypophysiotropic neurons ( gnrh1 or gnrh3 in the terminal nerve and the trigeminal nerve , gnrh2 in the midbrain tegmentum) occurs from the early developmental stages. Recent studies have suggested that non-hypophysiotropic GnRH neurons play various functional roles. Here, we summarize their anatomical/physiological properties and discuss their possible functions, focusing on studies in vertebrates. GnRH neurons in the terminal nerve show different spontaneous firing properties during the developmental stages. These neurons in adulthood show regular pacemaker firing, and it has been suggested that these neurons show neuromodulatory function related to the regulation of behavioral motivation, etc. In addition to their recognized role in neuromodulation in adult, in juvenile fish, these neurons, which show more frequent burst firing than in adults, are suggested to have novel functions. GnRH neurons in the midbrain tegmentum show regular pacemaker firing similar to that of the adult terminal nerve and are suggested to be involved in modulations of feeding (teleosts) or nutrition-related sexual behaviors (musk shrew). GnRH neurons in the trigeminal nerve are suggested to be involved in nociception and chemosensory avoidance, although the literature on their electrophysiological properties is limited. Sympathetic preganglionic cells in the spinal cord were first reported as peptidergic modulatory neurons releasing GnRH with a putative function in coordinating interaction between vasomotor and exocrine outflow in the sympathetic nervous system. The functional role of non-hypophysiotropic GnRH neurons may thus be in the global modulation of neural circuits in a manner dependent on internal conditions or the external environment.

PACAP Induces Light Aversion in Mice by an Inheritable Mechanism Independent of CGRP

“…RNAs for the gonadotropin hormones FSH and LH, along with the receptor that controls their release (GnRHR) were elevated in a subset of males. These proteins are most often viewed in the context of their regulation of gonadal hormones, however expression of gonadotropin releasing hormone has been reported in trigeminal ganglia neurons believed to be involved in nociception and chemosensory avoidance (Umatani and Oka, 2019). Increased expression of GnRHR in responder mice could thus enhance a local positive feedback loop.…”

The gonadotropin-releasing hormones: Lessons from fish

“…In fish with two Gnrh forms, one Gnrh variant (Gnrh3 in zebrafish, cyprinids and salmonids and Gnrh1 in catfish and eel), which is expressed both in the OB/TN and POA, is the more abundant form in the pituitary and its levels correlate with gonadal development (see for review Goos et al, 1997;Amano et al, 1997;Kah et al, 2007;Choi, 2018). Nevertheless, evidence obtained in several species suggests that OB/TN cells rarely project to the pituitary (Umatani and Oka, 2019).…”

Fish reproductive biology – Reflecting on five decades of fundamental and translational research

“…The OB/TN GnRH3 has been implicated in transducing external cues, such as olfaction and social information (pheromones) to reproductive processes (Ueda et al, 2016;Munoz-Cueto 2020). Additionally, the multiplicity of GnRHs across fish and vertebrate species has raised many interesting evolutionary questions that were addressed by several excellent reviews (Okubo and Nagahama, 2008;Kah et al, 2007;Roch et al, 2011Roch et al, , 2014Lovejoy et al, 2018;Choi 2018;Umatani and Oka, 2019;Dufour et al, 2020;Kah, 2020;Munoz-Cueto et al, 2001;Trudeau and Somoza, 2020).…”