Excitatory effects of the puberty-initiating peptide kisspeptin and group I metabotropic glutamate receptor agonists differentiate two distinct subpopulations of gonadotropin-releasing hormone neurons.
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.
Dumalska
Iryna
I
Department of Psychiatry, Yale University School of Medicine and Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, Connecticut 06508, USA.
Wu
Min
M
Morozova
Elena
E
Liu
Rongjian
R
van den Pol
Anthony
A
Alreja
Meenakshi
M
D000818:Animals; D017609:Barium Compounds / Q000494:pharmacology; D002196:Capillaries / Q000294:innervation; D002712:Chlorides / Q000494:pharmacology; D020667:Diagonal Band of Broca / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D004351:Drug Resistance; D004594:Electrophysiology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics; D066298:In Vitro Techniques; D008297:Male; D008473:Median Eminence / Q000098:blood supply / Q000294:innervation; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000145:classification* / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D013569:Synapses / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000494:pharmacology*; D050599:Vesicular Glutamate Transport Protein 2 / Q000235:genetics
D017609:Barium Compounds; D002712:Chlorides; D015221:Potassium Channels; D012333:RNA, Messenger; D018094:Receptors, Metabotropic Glutamate; D025521:Tumor Suppressor Proteins; D050599:Vesicular Glutamate Transport Protein 2; C024986:barium chloride; D049452:Green Fluorescent Proteins; D007987:Gonadotropin-Releasing Hormone; D008734:Methoxyhydroxyphenylglycol; C010117:3,4-dihydroxyphenylglycol