Abstract
Activation of the G-protein-coupled receptor GPR54 by kisspeptins during normal puberty promotes the central release of gonadotropin-releasing hormone (GnRH) that, in turn, leads to reproductive maturation. In humans and mice, a loss of function mutations of GPR54 prevents the onset of puberty and leads to hypogonadotropic hypogonadism and infertility. Using electrophysiological, morphological, molecular, and retrograde-labeling techniques in brain slices prepared from vGluT2-GFP and GnRH-GFP mice, we demonstrate the existence of two physiologically distinct subpopulations of GnRH neurons. The first subpopulation is comprised of septal GnRH neurons that colocalize vesicular glutamate transporter 2 and green fluorescent protein and is insensitive to metabotropic glutamate receptor agonists, but is exquisitely sensitive to kisspeptin which closes potassium channels to dramatically initiate a long-lasting activation in neurons from prepubertal and postpubertal mice of both sexes. A second subpopulation is insensitive to kisspeptin but is uniquely activated by group I metabotropic glutamate receptor agonists. These two physiologically distinct classes of GnRH cells may subserve different functions in the central control of reproduction and fertility.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Barium Compounds / pharmacology
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Capillaries / innervation
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Chlorides / pharmacology
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Diagonal Band of Broca / cytology
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Diagonal Band of Broca / metabolism
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Diagonal Band of Broca / physiology
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Drug Resistance
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Electrophysiology
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Female
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Gonadotropin-Releasing Hormone / genetics
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Gonadotropin-Releasing Hormone / metabolism*
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Green Fluorescent Proteins / genetics
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In Vitro Techniques
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Male
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Median Eminence / blood supply
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Median Eminence / innervation
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Methoxyhydroxyphenylglycol / analogs & derivatives
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Methoxyhydroxyphenylglycol / pharmacology
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Mice
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Mice, Transgenic
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Neurons / classification*
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Neurons / drug effects
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Neurons / metabolism
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Neurons / physiology*
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Potassium Channels / drug effects
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Potassium Channels / metabolism
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RNA, Messenger / metabolism
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Rats
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Rats, Sprague-Dawley
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Receptors, Metabotropic Glutamate / agonists*
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Synapses / physiology
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Tumor Suppressor Proteins / pharmacology*
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Vesicular Glutamate Transport Protein 2 / genetics
Substances
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Barium Compounds
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Chlorides
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Potassium Channels
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RNA, Messenger
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Receptors, Metabotropic Glutamate
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Tumor Suppressor Proteins
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Vesicular Glutamate Transport Protein 2
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barium chloride
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Green Fluorescent Proteins
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Gonadotropin-Releasing Hormone
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Methoxyhydroxyphenylglycol
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3,4-dihydroxyphenylglycol