Evidence to suggest that gonadotropin-releasing hormone inhibits its own secretion by affecting hypothalamic amino acid neurotransmitter release.
The mediobasal hypothalamus of rats contains gonadotropin-releasing hormone (GnRH) receptors. These hypothalamic neurons also express the GnRH corresponding gene. Under these circumstances, the possibility exists that these GnRH receptors could be localized in other neurons, which are GnRH-receptive, unknowing the neurotransmitter quality. Therefore, we studied the in vitro effects of the GnRH agonist buserelin on GnRH, glutamate, gamma-amino-butyric acid (GABA) and taurine release from explanted superfused hypothalami of untreated and buserelin-pretreated (down-regulated) male rats. When buserelin was added to the superfusion medium it inhibited promptly the release of GnRH and the excitatory amino acid neurotransmitter glutamate, but stimulated the release of the inhibitory neurotransmitters, GABA and taurine. Hypothalamic release of GnRH from hypothalami collected from buserelin-treated (30 micrograms/100 g b.w. twice daily for 4 days) male rats released significantly less GnRH, glutamate and more GABA and taurine. The inhibitory effect of buserelin was maintained when the superfusion medium continuously contained the GnRH analog. When superfusion of hypothalami from buserelin-pretreated animals was performed in the absence of buserelin, GnRH and glutamate release increased significantly within 45-60 min, whereas GABA and taurine release decreased at this time point. When buserelin was added to the superfusion medium 2 h after buserelin-free superfusion, GnRH and glutamate release decreased whereas GABA and taurine release increased instantaneously. Buserelin-treated rats showed significantly low values of LH and testosterone than the untreated rats. These results suggest that GnRH receptors may not only be present in GnRH axon terminals in the median eminence, but also on glutamatergic, GABAergic and taurinergic neurons by which GnRH may exert an autoinhibitory ultrashort loop feedback on its own secretion. This effect appears to be connected with glutamatergic, GABAergic and taurinergic neurons.
Department of Physiology, Faculty of Medicine, University of Buenos Aires, Argentina.
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C
Feleder
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Jarry
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Leonhardt
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Moguilevsky
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Wuttke
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D002064:Buserelin / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013654:Taurine / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000596:Amino Acids; D018377:Neurotransmitter Agents; D013654:Taurine; D007987:Gonadotropin-Releasing Hormone; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D002064:Buserelin