scholarly journals Benzo[a]pyrene impairs the migratory pattern of human gonadotropin-releasing-hormone-secreting neuroblasts

2021 ◽  
Vol 65 (s1) ◽  
Author(s):  
Giulia Guarnieri ◽  
Matteo Becatti ◽  
Paolo Comeglio ◽  
Linda Vignozzi ◽  
Mario Maggi ◽  
...  
Keyword(s):  
Mrna Level ◽  
Reproductive Function ◽  
Gonadotropin Releasing Hormone ◽  
Human Reproduction ◽  
Gnrh Neuron ◽  
Releasing Hormone ◽  
Endocrine Disrupting Compound ◽  
Endocrine Disrupting ◽  
Migratory Pattern ◽  
Migratory Process

Benzo[a]pyrene (BaP) is a widespread pollutant that can act as an endocrine disrupting compound (EDC) and interferes with reproductive function. The central regulatory network of the reproductive system is mediated by gonadotropin-releasing hormone (GnRH) neurons, which originate in the olfactory placode and, during ontogenesis, migrate into the hypothalamus. Given the importance of the migratory process for GnRH neuron maturation, we investigated the effect of BaP (10 µM for 24 h) on GnRH neuroblasts isolated from the human fetal olfactory epithelium (FNCB4). BaP exposure significantly reduced the mRNA level of genes implicated in FNCB4 cell migration and affected their migratory ability. Our findings demonstrate that BaP may interfere with the central neuronal network controlling human reproduction affecting GnRH neuron maturation.

scholarly journals Distinct Mechanisms Involving Diverse Histone Deacetylases Repress Expression of the Two Gonadotropin β-Subunit Genes in Immature Gonadotropes, and Their Actions Are Overcome by Gonadotropin-Releasing Hormone

2007 ◽  
Vol 27 (11) ◽  
pp. 4105-4120 ◽  
Author(s):  
Stefan Lim ◽  
Min Luo ◽  
Mingshi Koh ◽  
Meng Yang ◽  
Mohammed Nizam bin Abdul Kadir ◽  
...  
Keyword(s):  
Histone Deacetylases ◽  
Reproductive Function ◽  
Gonadotropin Releasing Hormone ◽  
Β Subunit ◽  
Releasing Hormone ◽  
Calcium Calmodulin Dependent ◽  
Gnrh Release ◽  
Dependent Protein ◽  
Reproductive Cycles ◽  
Class Iia Hdacs

ABSTRACT The gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are produced in the embryonic pituitary in response to delivery of the hypothalamic gonadotropin releasing hormone (GnRH). GnRH has a pivotal role in reestablishing gonadotropin levels at puberty in primates, and for many species with extended reproductive cycles, these are reinitiated in response to central nervous system-induced GnRH release. Thus, a clear role is evident for GnRH in overcoming repression of these genes. Although the mechanisms through which GnRH actively stimulates LH and FSH β-subunit (FSHβ) gene transcription have been described in some detail, there is currently no information on how GnRH overcomes repression in order to terminate reproductively inactive stages. We show here that GnRH overcomes histone deacetylase (HDAC)-mediated repression of the gonadotropin β-subunit genes in immature gonadotropes. The repressive factors associated with each of these genes comprise distinct sets of HDACs and corepressors which allow for differentially regulated derepression of these two genes, produced in the same cell by the same regulatory hormone. We find that GnRH activation of calcium/calmodulin-dependent protein kinase I (CaMKI) plays a crucial role in the derepression of the FSHβ gene involving phosphorylation of several class IIa HDACs associated with both the FSHβ and Nur77 genes, and we propose a model for the mechanisms involved. In contrast, derepression of the LH β-subunit gene is not CaMK dependent. This demonstration of HDAC-mediated repression of these genes could explain the temporal shut-down of reproductive function at certain periods of the life cycle, which can easily be reversed by the actions of the hypothalamic regulatory hormone.

scholarly journals The cryptic gonadotropin-releasing hormone neuronal system of human basal ganglia

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Katalin Skrapits ◽  
Miklós Sárvári ◽  
Imre Farkas ◽  
Balázs Göcz ◽  
Szabolcs Takács ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Basal Forebrain ◽  
Gonadotropin Releasing Hormone ◽  
Human Reproduction ◽  
Projection Neurons ◽  
Marker Enzyme ◽  
Neuronal System ◽  
Releasing Hormone ◽  
Cholinergic Interneurons ◽  
Gnrh Neurons

Human reproduction is controlled by ~2,000 hypothalamic gonadotropin-releasing hormone (GnRH) neurons. Here we report the discovery and characterization of additional ~150,000-200,000 GnRH-synthesizing cells in the human basal ganglia and basal forebrain. Nearly all extrahypothalamic GnRH neurons expressed the cholinergic marker enzyme choline acetyltransferase. Similarly, hypothalamic GnRH neurons were also cholinergic both in embryonic and adult human brains. Whole-transcriptome analysis of cholinergic interneurons and medium spiny projection neurons laser-microdissected from the human putamen showed selective expression of GNRH1 and GNRHR1 autoreceptors in the cholinergic cell population and uncovered the detailed transcriptome profile and molecular connectome of these two cell types. Higher-order non-reproductive functions regulated by GnRH under physiological conditions in the human basal ganglia and basal forebrain require clarification. The role and changes of GnRH/GnRHR1 signaling in neurodegenerative disorders affecting cholinergic neurocircuitries, including Parkinson's and Alzheimer's diseases, need to be explored.

scholarly journals The cryptic gonadotropin-releasing hormone neuronal system of human basal ganglia

2021 ◽  
Author(s):  
Katalin Skrapits ◽  
Miklós Sárvári ◽  
Imre Farkas ◽  
Balázs Göcz ◽  
Szabolcs Takács ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Basal Forebrain ◽  
Cell Types ◽  
Gonadotropin Releasing Hormone ◽  
Human Reproduction ◽  
Projection Neurons ◽  
Neuronal System ◽  
Releasing Hormone ◽  
Cholinergic Interneurons ◽  
Gnrh Neurons

Human reproduction is controlled by ~2,000 hypothalamic gonadotropin-releasing hormone (GnRH) neurons. Here we report the discovery and characterization of additional 150-200,000 GnRH-synthesizing cells in the human basal ganglia and basal forebrain. Extrahypothalamic GnRH neurons were cholinergic. Though undetectable in adult rodents, the GnRH-GFP transgene was expressed transiently by caudate-putamen cholinergic interneurons in newborn transgenic mice. In slice electrophysiological studies, GnRH inhibited these interneurons via GnRHR1 autoreceptors. Whole-transcriptome analysis of cholinergic interneurons and medium spiny projection neurons laser-microdissected from the human putamen confirmed selective expression of GnRH and GnRHR1 autoreceptors in cholinergic cells and uncovered the detailed transcriptome profile and molecular connectome of these two cell types. Higher-order non-reproductive functions regulated by GnRH under physiological conditions in the human basal ganglia and basal forebrain require clarification. GnRH/GnRHR1 signaling as a potential therapeutic target in the treatment of neurodegenerative disorders affecting cholinergic neurocircuitries, including Parkinson’s and Alzheimer’s diseases, needs to be explored.

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