A second isoform of gonadotropin‐releasing hormone is present in the brain of human and rodents

Chen, Alon; Yahalom, Dror; Ben-Aroya, Nurit; Kaganovsky, Ella; Okon, E; Koch, Yitzhak

doi:10.1016/s0014-5793(98)01064-3

Cited by 100 publications

(76 citation statements)

References 51 publications

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“…GNRH, the ligand for GNRHR, is detected in humans in two forms, named GNRH1 and GNRH2, which are coded by two different genes (24). While GNRH1 is mainly expressed in the hypothalamus, GNRH2 is expressed at significantly higher levels outside the brain, particularly in the kidney, bone marrow, and prostate (25).…”

Section: Discussionmentioning

confidence: 99%

A case of primary aldosteronism in pregnancy: do LH and GNRH receptors have a potential role in regulating aldosterone secretion?

Albiger¹,

Sartorato²,

Mariniello³

et al. 2011

European Journal of Endocrinology

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Objective: The mechanisms inducing steroidogenesis in primary aldosteronism (PA) remain poorly defined. It was recently demonstrated that some G-protein-coupled receptors are abnormally expressed in aldosterone-producing adenomas (APA). We evaluated the potential role of LH and GNRH receptors (LHR (or LHCGR) and GNRHR) in regulating aldosterone secretion in a patient with APA arising during pregnancy (index case) and in a subset of other patients with PA. Patients and methods: GNRH test was performed in the index case, 11 other PA, and 5 controls. GNRHR and LHR expressions were examined in 23 APA and 6 normal tissues. Results: Aldosterone response increased significantly (114%) in the index case after GNRH test was performed preoperatively, while it was blunted after adrenalectomy. Aldosterone also increased after human chorionic gonadotropin and triptorelin stimulation. A partial aldosterone response to GNRH was observed in other 7/11 PA, while a significant response was observed in two patients. Controls did not respond to GNRH test. GNRHR was overexpressed and LHR expression was moderate in the APA tissue from the index case. Moreover, LHR was found in normal adrenals and overexpressed in 6/22 APA. GNRHR was overexpressed in 6/22 APA, 2 of them with a 95-and 109-fold higher expression than normal. A correlation between the clinical and molecular findings was observed in five out of seven patients. Conclusion: We describe a case of PA diagnosed during pregnancy, which appeared to correlate with aberrant LHR and GNRHR expression. Our findings suggest that a subset of patients with PA has aberrant LHR and GNRHR expression, which could modulate aldosterone secretion.

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Section: Discussionmentioning

confidence: 99%

A case of primary aldosteronism in pregnancy: do LH and GNRH receptors have a potential role in regulating aldosterone secretion?

Albiger¹,

Sartorato²,

Mariniello³

et al. 2011

European Journal of Endocrinology

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“…Conversely, in the hypogonadal mouse lacking m-LHRH, c-GnRH-II cells have been detected in the arcuate nucleus. Since the c-GnRH-II antiserum was conjugated to BSA (25) and because the study does not indicate that the anti-BSA activity was absorbed (26), these putative c-GnRH-II cells found in the arcuate nucleus may represent BSA stained cells by the anti-BSA antibodies within the antiserum and not c-GnRH-II neurons. Similar false-positive results for the localization of GnRH have been previously demonstrated by using an antiserum generated against GnRH-BSA hapten-conjugates (27).…”

Section: Discussionmentioning

confidence: 99%

Gonadotropin-releasing hormone neurons in the preoptic-hypothalamic region of the rat contain lamprey gonadotropin-releasing hormone III, mammalian luteinizing hormone-releasing hormone, or both peptides

Hiney¹,

Sower²,

Yu³

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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This study utilized a newly developed antiserum, specific for lamprey gonadotropin-releasing hormone III (l-GnRH-III), to determine the following: in which regions of the rat hypothalamus the neuronal perikarya producing l-GnRH-III are localized; and whether this peptide, known to selectively induce follicle-stimulating hormone release, is coexpressed in neurons containing mammalian luteinizing hormone-releasing hormone (m-LHRH). Double-label immunocytochemistry was performed by using an l-GnRH-III polyclonal antiserum and an LHRH monoclonal antiserum. Immunopositive neurons for l-GnRH-III, m-LHRH, or neurons coexpressing both peptides were detected within the organum vasculosum lamina terminalis (OVLT) region of the preoptic area (POA). Caudal to the OVLT, l-GnRH-III-positive neurons were also observed dorsomedially, above the third ventricle in the medial POA. The m-LHRH neurons were not observed in this area. The lateral POA region contained neurons positive for both peptides along with singlelabeled neurons for each peptide. Importantly, neurons that expressed l-GnRH-III, m-LHRH, or both peptides were also detected in the ventral regions of the rostral hypothalamus, dorsolateral to the borders of the supraoptic nuclei. In both of these latter areas, neurons containing l-GnRH-III were slightly dorsal to neurons containing only m-LHRH. The l-GnRH-III perikarya and fibers were eliminated by absorption of the primary antiserum with l-GnRH-III, but not by l-GnRH-I, chicken-GnRH-II, or m-LHRH. These results indicate that, unlike other isoforms of GnRH found in the mammalian brain, l-GnRH-III neurons not only are observed in regions that control follicle-stimulating hormone release but also are colocalized with m-LHRH neurons in areas primarily controlling LH release. These findings suggest an interrelationship between these two peptides in the control of gonadotropin secretion.onadotropin-releasing hormones (GnRHs) have been detected in all vertebrate species studied across the phylogenetic scale from tunicates (1, 2) to humans (2, 3). In mammals, the prevailing view is that luteinizing hormone (LH) and folliclestimulating hormone (FSH) release is primarily controlled by mammalian luteinizing hormone-releasing hormone (m-LHRH). However, recent studies have uncovered other isoforms of the GnRH peptide besides m-LHRH in the mammalian brain (3-8). Chicken-GnRH-II (c-GnRH-II) (4-7) and lampreyGnRH (l-GnRH; refs. 3 and 8) have been detected in the mammalian hypothalamus. Specifically, in situ hybridization experiments localized c-GnRH-II mRNA in the supraoptic, paraventricular, and suprachiasmatic nuclei as well as in the medial basal hypothalamus, but this mRNA was not detected within neurons that were immunopositive for m-LHRH (5). With regard to l-GnRH, an antiserum to l-GnRH-I bound to cells and nerve fibers projecting through the arcuate nucleus and terminating in the median eminence (ME) in the human brain (3). Additionally, our recent study using an antibody that recognized both l-GnRH-I and l-GnRH-III allowed u...

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“…The GnRH II gene in the human brain is expressed mainly in the periaqueductal region of the midbrain (Chen et al, 1998), high in the caudate nucleus and, to a lesser extent, in the hippocampus and amygdala (White et al, 1998 The human placenta expresses GnRH I mRNA in vitro and secretes the GnRH I decapeptide, which is identical with that synthesized in the hypothalamus (Siler- Khodr and Khodr, 1979;Khodr and Siler-Khodr, 1980). Expression of GnRH I mRNA has been demonstrated in all human uterine compartments (Irmer et al, 1994;Chegini et al, 1996;Kobayashi et al, 1997;Dong et al, 1998;Raga et al, 1998;Cheng and Leung, 2005).…”

Section: Gnrh and Its Genementioning

confidence: 99%

Evolution of gonadotropin-releasing hormone (GnRH) structure and its receptor

Kochman¹

2012

J. Anim. Feed Sci.

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It is evident now that the gonadotropin-releasing hormone (GnRH) structure was already in existence very early in the evolution of animals and was co-opted in diverse ways to regulate reproduction. During 600 million years of animal evolution, the N and C termini of GnRH have been conserved as functional domains for binding and activating cognate receptors to accomplish its functions. About 400 millions years ago, a single substitution of the chiral amino acid in position 6 of GnRH in jawless fish by the achiral glycine facilitated a type II' β-turn conformation of GnRH to allow spatially close interaction of functional domains of GnRH with receptors, in contrast to the interaction of more extended GnRH structures with their cognate receptors in earlier-evolved species. GnRH II was preconfigured to this conformation through intramolecular interactions, which accounts for its high binding affinity and total conservation of primary structure over 400 million years of evolution. It is very surprising and fascinating that the coordinated evolutionary selection of amino acids participating in binding GnRH has resulted in such perfection, that no substitution with a natural amino acid in any position improves binding potency.

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A second isoform of gonadotropin‐releasing hormone is present in the brain of human and rodents

Cited by 100 publications

References 51 publications

A case of primary aldosteronism in pregnancy: do LH and GNRH receptors have a potential role in regulating aldosterone secretion?

A case of primary aldosteronism in pregnancy: do LH and GNRH receptors have a potential role in regulating aldosterone secretion?

Gonadotropin-releasing hormone neurons in the preoptic-hypothalamic region of the rat contain lamprey gonadotropin-releasing hormone III, mammalian luteinizing hormone-releasing hormone, or both peptides

Evolution of gonadotropin-releasing hormone (GnRH) structure and its receptor

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