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Burst firing of neurons optimizes neurotransmitter release. GnRH neurons exhibit burst firing activity and T-type calcium channels, which are vital for burst firing activity, are regulated by 17β-estradiol (E2) in GnRH neurons. To further elucidate ion channel expression and E2 regulation during positive and negative feedback on GnRH neurosecretion, we used single cell RT-PCR and real-time qPCR to quantify channel mRNA expression in GnRH neurons. GFP-GnRH neurons expressed numerous ion channels important for burst firing activity. E2-treatment sufficient to induce an LH surge increased mRNA expression of HCN1 channels, which underlie the pacemaker current, the calcium-permeable Ca(V)1.3, Ca(V)2.2, Ca(V)2.3 channels, and TRPC4 channels, which mediate the kisspeptin excitatory response. E2 also decreased mRNA expression of SK3 channels underlying the medium AHP current. Therefore, E2 exerts fundamental changes in ion channel expression in GnRH neurons, to prime them to respond to incoming stimuli with increased excitability at the time of the surge.
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http://dx.doi.org/10.1016/j.mce.2012.12.021 | DOI Listing |
Stem Cell Rev Rep
September 2025
Stem Cells and Metabolism Research Program (STEMM), Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, 00014, Finland.
Mutations in Delta Like Non-Canonical Notch Ligand 1 (DLK1), a paternally expressed imprinted gene, underlie central precocious puberty (CPP), yet the mechanism remains unclear. To test the hypothesis that DLK1 plays a role in gonadotropin releasing hormone (GnRH) neuron ontogeny, 75 base pairs were deleted in both alleles of DLK1 exon 3 with CRISPR-Cas9 in human pluripotent stem cells (hPSCs). This line, exhibiting More than 80% loss of DLK1 protein, was differentiated into GnRH neurons by dual SMAD inhibition (dSMADi), FGF8 treatment and Notch inhibition, as previously described, however, it did not exhibit accelerated GNRH1 expression.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2025
Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China.
The onset of puberty is increasingly observed at earlier ages in children, especially in girls with obesity, a trend that predisposes them to long-term metabolic and reproductive disorders in adulthood. Bile acids have emerged as pivotal signaling molecules in both metabolic and reproductive disorders, but remain unexplored in the early onset of puberty in children. Herein, we find elevated levels of muricholic acid (MCA) species in the serum of girls with central precocious puberty, which strongly correlate with indices of hypothalamic-pituitary-gonadal axis activation and can reach peak levels during puberty among healthy children.
View Article and Find Full Text PDFFertil Steril
August 2025
Division of Reproductive Endocrinology and Infertility, Department Obstetrics and Gynaecology, Erasmus University Medical Center, Wytemaweg 80, 3015CE, Rotterdam, The Netherlands. Electronic address:
Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder among women of reproductive age, with a prevalence estimated between 10-13%. It is characterized by ovulatory dysfunction, hyperandrogenism, and polycystic ovarian morphology. Anti-Müllerian hormone (AMH) plays a key role in regulating normal reproductive function in both males and females.
View Article and Find Full Text PDFEndocrinology
August 2025
National Institute of Neurological Disorders and Stroke (NINDS)/National Institutes of Health (NIH), Bethesda, MD, United States.
Many clinical studies have identified correlations between thyroid dysfunction and reproductive issues, yet the underlying mechanisms behind this interaction remain poorly understood. In this study, we investigated the effect of T3 on the activity of GnRH neurons, a key regulator of the central reproductive axis. Dual labeling confirmed that GnRH neurons express thyroid receptor (TR)α and integrin αVβ3 receptors mediating genomic and non-genomic effects of thyroid hormones, respectively.
View Article and Find Full Text PDFJ Behav Brain Sci
February 2025
Departments of Neuroscience and Biology, Brown University, Providence, Rhode Island, USA.
Background: Neurodevelopmental abnormalities in experimental fetal alcohol spectrum disorder (FASD) are associated with impaired signaling through complex pathways that mediate neuronal survival, growth, migration, energy metabolism, and plasticity. Gestational dietary soy prevents alcohol-related impairments in placentation and FASD-associated fetal anomalies.
Objective: This study was designed to determine if gestational dietary soy would be sufficient to normalize cognitive function in young adolescent offspring after chronic in utero exposure to alcohol.