Gonadotropin-Inhibitory Hormone Inhibits Gonadal Development and Maintenance by Decreasing Gonadotropin Synthesis and Release in Male Quail

Abstract

Until recently, any neuropeptide that directly inhibits gonadotropin secretion had not been identified. We recently identified a novel hypothalamic dodecapeptide that directly inhibits gonadotropin release in quail and termed it gonadotropin-inhibitory hormone (GnIH). The action of GnIH on the inhibition of gonadotropin release is mediated by a novel G protein-coupled receptor in the quail pituitary. This new gonadotropin inhibitory system is considered to be a widespread property of birds and provides us with an unprecedented opportunity to study the regulation of avian reproduction from an entirely novel standpoint. To understand the physiological role(s) of GnIH in avian reproduction, we investigated GnIH actions on gonadal development and maintenance in male quail. Continuous administration of GnIH to mature birds via osmotic pumps for 2 wk decreased the expressions of gonadotropin common alpha and LHbeta subunit mRNAs in a dose-dependent manner. Plasma LH and testosterone concentrations were also decreased dose dependently. Furthermore, administration of GnIH to mature birds induced testicular apoptosis and decreased spermatogenic activity in the testis. In immature birds, daily administration of GnIH for 2 wk suppressed normal testicular growth and rise in plasma testosterone concentrations. An inhibition of juvenile molt also occurred after GnIH administration. These results indicate that GnIH inhibits gonadal development and maintenance through the decrease in gonadotropin synthesis and release. GnIH may explain the phenomenon of photoperiod-induced gonadal regression before an observable decline in hypothalamic GnRH in quail. To our knowledge, GnIH is the first identified hypothalamic neuropeptide inhibiting reproductive function in any vertebrate class.

Apoptosis-mediated testicular alteration in Japanese quail (Coturnix coturnix japonica) in response to temporal phase relation of serotonergic and dopaminergic oscillations

“…3). It may be the case that these two neuropeptides may, in combination, act on testicular development, maintenance and steroidogenesis (Ubuka et al, 2006(Ubuka et al, , 2013a.…”

“…This indicates apoptotic changes in the regressed testes along with increased expression of GnIH and weak immunoreactivity of GnRH-I, pro-caspase-3 and uncleaved/full-length PARP-1. Previous studies have shown that the suppression of hypothalamic GnRH system as well as the potentiation of GnIH may lead to the suppression of pituitary LH/FSH release and also suppresses endogenous testosterone production by the Leydig cells, resulting in germ cell apoptosis (Ubuka et al, 2006(Ubuka et al, , 2013a. As yet, however, the molecular mechanism by which germ cells undergo apoptosis is not understood.…”

“…Both spontaneous and increased cell death due to triggering stimuli such as increased GnIH, deprivation of testosterone and gonadotrophins, etc., occur via apoptosis. It is also well established that the seasonal testicular regression in photoperiodic birds is mediated by apoptosis ) and testicular apoptosis is mediated through the GnIH in quail (Ubuka et al, 2006). We hypothesized that the testicular regression in 8-h quail may be due to testicular apoptosis.…”

“…They also clearly demonstrated that GnIH and GnIH-R are expressed in the quail gonads and suggested that GnIH acts directly on the avian reproductive system . It is also reported that in vivo administration of GnIH decreases seminiferous tubule diameter and the number of germ cells in quail via suppression of pituitary gonadotropin synthesis and release (Ubuka et al, 2006). The presence of GnIH-R has been detected in the testes and ovaries of several vertebrate species, including birds (McGuire and Bentley, 2010), and putative GnIH binding sites have been demonstrated in the granulosa cell layer by receptor fluorography in birds .…”

A genetically female brain is required for a regular reproductive cycle in chicken brain chimeras

“…Plasma LH levels were determined by radioimmunoassay (RIA) using a highly purified chicken LH (USDA-cLH-I-3) 52 as the radioligand and standard, and polyclonal rabbit anti-chicken LH serum (USDA-AcLH-5) 52 supplied by the US Department of Agriculture-Agricultural Research Service (USDA-ARS), Biotechnology and Germplasm laboratory (Beltsville, MD). The RIA was performed as described previously 53,54 . The antiserum against chicken LH, at a final dilution of 1:50,000, exhibited the ability to specifically bind 23% of the added radioligand in the absence of any unlabelled chicken LH.…”