Regional Expression of mRNA Encoding a Second Form of Gonadotropin-Releasing Hormone in the Macaque Brain

Abstract

In mammals, reproduction is thought to be controlled by a single neuropeptide, gonadotropin-releasing hormone (GnRH-I), which regulates the synthesis and secretion of gonadotropins from the pituitary gland. However, another form of this decapeptide (GnRH-II), of unknown function, also exists in the brain of many vertebrate species, including humans; it is encoded by a different gene and its amino acid sequence is 70% identical to that of GnRH-I. Here we report the cloning of a GnRH-II cDNA from the rhesus macaque (Macaca mulatta), and show for the first time by in situ hybridization that GnRH-II mRNA is expressed in the primate midbrain, hippocampus and discrete nuclei of the hypothalamus, including the supraoptic, paraventricular, suprachiasmatic and arcuate. Because the regional distribution pattern of cells containing GnRH-II mRNA is largely dissimilar to that of cells containing GnRH-I mRNA, it is likely that these two cell populations receive distinct neuroendocrine inputs and thus regulate GnRH synthesis and release differently.

A novel mammalian receptor for the evolutionarily conserved type II GnRH

“…1 legend). In some of these areas (e.g., midbrain and supraoptic nucleus), the GnRH II ligand is also expressed (20,36). The distribution pattern of type II GnRH receptor-positive cells in extrahypothalamic regions overlapped with that of the early developing mammalian GnRH I cells we have described (19).…”

“…Moreover, GnRH II has been localized to the hypothalamic area in species of non-mammalian vertebrates (see refs. 7 and 8 for review) and the supraoptic, paraventricular, arcuate, and pituitary stalk regions of monkeys, where it is thought to play a role in gonadotropin secretion (20,36). We therefore conducted studies by using a well-established sheep model to determine the relative effects of mammalian GnRH I and GnRH II on LH and FSH secretion.…”

Biology of the gonadotropin-releasing hormone system in gynecological cancers

“…A similar situation seems to exist in mammals. One of these GnRH variants is GnRH-II (also called chicken GnRH-II), which is entirely conserved in structure in the evolution from fish to mammals (109,110). In human granulosaluteal cells, expression of GnRH-II has been found (111).…”

Contribution of Chicken GnRH-II and Lamprey GnRH-III on Gonadotropin Secretion

“…Among primates, the rhesus monkey (Macaca mulatta), is one of the few species studied to date that posses a functional cGnRH-II peptide and type II GnRHR (Stewart et al, 2009). In these species, cGnRH-II is expressed in the hypothalamic median eminence (Urbanski et al, 1999), and has the ability to stimulate gonadotropin secretion (Lescheid et al, 1997). The rhesus hypothalamic cells that express mGnRH and cGnRH-II have a differential distribution pattern.…”

“…The rhesus hypothalamic cells that express mGnRH and cGnRH-II have a differential distribution pattern. In contrast to mGnRH, the axonal projections of cGnRH-II have a direct input in the neural lobe of the pituitary gland, raising the possibility that both forms of GnRH may play different physiological roles in the regulation of gonadotropin secretion (Urbanski et al, 1999). When cultured pituitary cells form male rhesus monkeys were incubated with cGnRH-II, LH and FSH were significantly increased.…”