Gonadotropin-Releasing Hormone (GnRH)

Cross references:  Anterior Pituitary    Posterior Pituitary    HPA Axis   

Gonadotropin-releasing hormone (Wiki) 
    "Gonadotropin-releasing hormone (GnRH), also known as Luteinizing-hormone-releasing hormone (LHRH) and luliberin, is a tropic peptide hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. GnRH is synthesized and released from neurons within the hypothalamus. The peptide belongs to gonadotropin-releasing hormone family."  
GnRH is considered a neurohormone, a hormone produced in a specific neural cell and released at its neural terminal.  
    A key area for production of GNRH is the preoptic area of the hypothalamus, which contains most of the GnRH-secreting neurons.  
    GnRH neurons originate in the nose and migrate into the brain, where they are scattered throughout the medial septum and hypothalamus and connected by very long >1-millimeter-long dendrites. These bundle together so they receive shared synaptic input, a process that allows them to synchronize their GnRH release.[1]
    GnRH is secreted in the hypophysial portal bloodstream at the median eminence. The portal blood carries the GnRH to the pituitary gland, which contains the gonadotrope cells, where GnRH activates its own receptor, gonadotropin-releasing hormone receptor (GnRHR), a seven-transmembrane G-protein-coupled receptor that stimulates the beta isoform of Phosphoinositide phospholipase C, which goes on to mobilize calcium and protein kinase C.  
    This results in the activation of proteins involved in the synthesis and secretion of the gonadotropins LH and FSH. GnRH is degraded by proteolysis within a few minutes.
At the pituitary, GnRH stimulates the synthesis and secretion of the gonadotropins, follicle-stimulating hormone (FSH), and luteinizing hormone (LH). These processes are controlled by the size and frequency of GnRH pulses, as well as by feedback from androgens and estrogens. Low-frequency GnRH pulses lead to FSH release, whereas high-frequency GnRH pulses stimulate LH release.

GNRH1 structure.png


Phylogeny and ontogeny of gonadotropin-releasing hormone: comparison of guinea pig, rat, and a protochordate.
    "Immunoreactive gonadotropin-releasing hormone (ir-GnRH) was detected in brain extracts of newborn and 10-day-old rats and in adult guinea pigs; it was also present in extracts of the neural ganglion and gland of a protochordate. Radioimmunoassay (RIA) using different GnRH antisera after high-performance liquid chromatography (HPLC) revealed that the dominant form of GnRH is the mammalian form (pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2) both during ontogenesis in the rat and in the adult guinea pig known to have variant forms of other peptide hormones. None of the other forms of GnRH identified in nonmammalian species to date appear to be present in the rat or guinea pig. A small amount of an unidentified HPLC early eluting form of GnRH is present, but detection by antiserum B-6 implies that it is also mammalian GnRH, with the possibility of changes in positions 2-4. The molecular form of GnRH in a protochordate, the sea squirt Chelyosoma productum, is distinct from salmon and mammalian GnRHs. Cross-reactivity with the sea squirt GnRH-like molecule was highest with an antiserum made against lamprey GnRH; the same antiserum was used to stain nerve fibers in the neural ganglion and some of its roots. This is the first report using RIA, HPLC, and immunocytochemistry to show that protochordates have GnRH-like material. The results suggest that GnRH may have been present at the transition between the invertebrates and vertebrates."

Evolution of neuroendocrine peptide systems: gonadotropin-releasing hormone and somatostatin.   
Nine vertebrate and two protochordate gonadotropin-releasing hormone (GnRH) decapeptides have been identified and sequenced. Multiple molecular forms of GnRH peptide were present in the brain of most species examined, and cGnRH-II generally coexists with one or more GnRH forms in all the major vertebrate groups. The presence of multiple GnRH forms has been further confirmed by the deduced GnRH peptide structure from cDNA and/or gene sequences in several teleost species and tree shrew. High conservation of the primary structure of GnRH decapeptides and the overall structure of GnRH genes and precursors suggests that they are derived from a common ancestor. Somatostatin (SRIF) is a phylogenetically ancient, multigene family of peptides. A tetradecapeptide, SRIF (SRIF14) has been conserved, with the same amino acid sequence, in representative species of all classes of vertebrate. Four molecular variants of SRIF14 have been identified. SRIF14 is processed from preprosomatostatin-I, which contains SRIF14 at its C-terminus; preprosomatostatin-I is also processed to SRIF28 in mammals and SRIF26 in bowfin. Teleost fish possess a second somatostatin precursor, preprosomatostatin-II, containing [Tyr7, Gly10]-SRIF14 at the C-terminus, that is mainly processed into large forms of SRIF."  

Gonadotropin-releasing hormone        
    See:  Hemichordate Hormones

Induction of gamete release by GnRH (PubMed)       
Only abstract available online. 
Gonadotropin-releasing hormone (GnRH) of vertebrates is now believed to have multiple functions in addition to its role as a hypophysiotropic hormone, as originally defined.  
    Recently, it has been shown that GnRH occurs also in the ascidians, which are considered ancestral chordates.  Here the author shows that GnRH induces spawning of gametes from mature individuals of Ciona intestinalis.  
    Ciona accumulates mature gametes in the gonoducts and maintains them until spawning is triggered by a photoperiodic cue(s). Injection of synthetic tunicate GnRH-I or -II into various sites of mature individuals effectively induced gamete release (spawning), although the former was more potent.  
    Gamete release often occurred on a larger scale than in spontaneous spawning. However, moderate gamete release, similar to spontaneous spawning, was often triggered by exogenous tunicate GnRH.  
    GnRH in vivo apparently is released from the GnRH-containing neurons that are distributed from the region of the cerebral ganglion to the proximal part of the ovary along the dorsal strand within the blood sinus; this indicates that both forms of tunicate GnRH may be the actual inducers of spawning.  
    It is suggested that, in the ancestral chordate, GnRH neurons release GnRH prior to the spawning and the released GnRH acts directly on the epithelium of gonoducts or functions as a neuromodulator of other neurons innervating the gonoducts to induce spawning.

2009    35<72 
Characterization and putative role of a type I gonadotropin-releasing hormone in the cephalochordate amphioxus.   
Employing reverse-phase chromatography, we purified a peptide of relative molecular mass of 1182.60 Da from the cephalochordate amphioxus Branchiostoma lanceolatum. We found that its amino acid sequence (pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH(2)) was identical to that of mammalian GnRH."  

2014    12<73 
At the transition from invertebrates to vertebrates, a novel GnRH-like peptide emerges in amphioxus. 
In the amphioxus, an invertebrate that provides the best model for the transition to vertebrates, four GnRH receptors (GnRHRs) were previously described, but their native ligands were not identified. ... we identified the first GnRH-like peptide confirmed in the amphioxus Branchiostoma floridae"  

2014    10<73 
GnRH receptors and peptides: skating backward. 
The invertebrate deuterostomes (echinoderms, hemichordates and amphioxus) have derived GnRH-like peptides, although one amphioxus GnRH with a syntenic relationship to human GnRHs has been shown to be functional. Phylogenetic analysis suggests that gene duplications in the ancestral bilaterian produced two receptor types, one of which became adipokinetic hormone receptor/GnRHR and the other corazonin receptor/invGnRHR. It appears that the ancestral deuterostome had both a GnRHR and invGnRHR, and this is still the case in amphioxus."  

2015    5<73 

An evolutionary scenario for gonadotrophin-inhibitory hormone in chordates. 
More recently, we identified a novel gene encoding RFamide peptides in the amphioxus. Molecular phylogenetic analysis and synteny analysis indicated that this gene is closely related to the genes of GnIH and NPFF of vertebrates. The results suggest that the identified protochordate gene is similar to the common ancestor of GnIH and NPFF genes, indicating that the origin of GnIH and NPFF may date back to the time of the emergence of early chordates. The GnIH and NPFF genes may have diverged by whole-genome duplication during the course of vertebrate evolution. "  

An evolutionary scenario for gonadotrophin-inhibitory hormone in chordates.