ESPEYB19 7. Puberty Basic Science (7 abstracts)
7.10. The cryptic gonadotropin-releasing hormone neuronal system of human basal ganglia
Skrapits K , Sárvári M , Farkas I , Göcz B , Takács S , Rumpler É , Váczi V , Vastagh C , Rácz G , Matolcsy A , Solymosi N , Póliska S , Tóth B , Erdélyi F , Szabó G , Culler MD , Allet C , Cotellessa L , Prévot V , Giacobini P & Hrabovszky E
Elife. 2021 Jun 15;10:e67714. doi: 10.7554/eLife.67714. PMID: 34128468https://elifesciences.org/articles/67714
Brief Summary: This histological and transcriptomic study evaluates the presence and the potential role of extra-hypothalamic GnRH neurons in humans and identifies cholinergic GnRH-synthesizing cells in the human basal ganglia and basal forebrain.
Hypothalamic GnRH neurons originate from the olfactory placodes and migrate through a ventral path to the hypothalamus, where they control reproduction [1]. Studies have identified a dorsal migration pathway of GnRH neurons to the pallial and/or subpallial brain structures [2],[3] as well as expression of GnRH mRNA/immune-reactivity in extra-hypothalamic regions not related to reproduction both in humans and non-human primates [4],[5].
This study confirmed the presence of extra-hypothalamic GnRH (eh-GNRH) neurons in the human brain and evaluated their function. The authors identified almost 150,000-200,000 eh-GnRH neurons located in the basal ganglia and forebrain of the human brain. The putamen (Pu) contains most of these cells (82%), while other regions included the nucleus accumbens, caudate nucleus (Cd) and nucleus basalis magnocellularis (nbM). These neurons secreted authentic GnRH decapeptide derived from the GNRH1 transcript, while its metabolite GNRH1-5 was present at lower levels. They express choline acetyltransferase (ChAT). Surprisingly, the ChAT phenotype was also present in 34.6% of hypothalamic GnRH neurons, a phenomenon not observed in other species before. The authors also showed that GnRH neurons become cholinergic after entering the brain.
This fascinating study reveals the complexity of the GnRH system beyond its reproductive function and opens new avenues regarding the potential role of such GnRH neurons in neurodegenerative diseases affecting cholinergic circuits. Symptoms in Alzheimer’s disease for instance are due to the loss of basal forebrain cholinergic neurons, some of which show GnRH immune-reactivity. Additionally, the whole-transcriptome analysis of cholinergic inter-neurons dissected from the putamen could identify some alternative pathways to counteract the hyperactivity of cholinergic neurons, which explains some treatment-resistant symptoms in Parkinson’s disease.
References: 1. Casoni F, Malone SA, Belle M, Luzzati F, Collier F, Allet C, Hrabovszky E, Rasika S, Prevot V, Chédotal A, Giacobini P. (2016) “Development of the neurons controlling fertility in humans: new insights from 3D imaging and transparent fetal brains.” Development.; 143(21):3969–3981. 2. Rance NE, Young WS, McMullen NT. (1994) “Topography of neurons expressing luteinizing hormone-releasing hormone gene transcripts in the human hypothalamus and basal forebrain,” J Comp Neurol.; 339(4):573–86. 3. Krajewski SJ, Abel TW, Voytko ML, Rance NE. (2003) “Ovarian steroids differentially modulate the gene expression of gonadotropin-releasing hormone neuronal subtypes in the ovariectomized cynomolgus monkey,” J Clin Endocrinol Metab.; 88(2):655–62. 4. Terasawa E, Busser BW, Luchansky LL, Sherwood NM, Jennes L, Millar RP, Glucksman MJ, Roberts JL. (2001) “Presence of luteinizing hormone-releasing hormone fragments in the rhesus monkey forebrain.” J Comp Neurol.; 439(4):491–504. 5. Quanbeck C, Sherwood NM, Millar RP, Terasawa E. (1997) “Two populations of luteinizing hormone-releasing hormone neurons in the forebrain of the rhesus macaque during embryonic development,” J Comp Neurol. 1997 Apr 14; 380(3):293–309.
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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