Pulsatile release of gonadotropin-releasing hormone (GnRH) from the rat hypothalamus in vitro: calcium and glucose dependency and inhibition by superactive GnRH analogs.
We have shown previously that the rat hypothalamus retains in vitro its capacity of generating pulsatile release of GnRH. The present study evaluated if pulsatile release of GnRH in vitro was influenced by metabolic conditions (calcium and glucose availability) and the possible self-regulatory role of GnRH in its pulsatile secretion. In the presence of a calcium-chelating agent (EGTA, 20 mM) or a calcium-channel blocker (D-600, 0.1 mM), the release of GnRH induced by a depolarization (veratridine, 50 microM) was markedly and reversibly decreased. In addition, frequency and amplitude of GnRH secretory pulses were significantly reduced (P less than 0.05). When glucose use was inhibited using 2-deoxyglucose (5.6 mM) the release of GnRH induced by veratridine and the frequency of GnRH pulses were also blunted (P less than 0.05). Superactive agonists of GnRH (Buserelin and D-TRP6-PRO9-N-ET, 10 nM) caused a prompt decrease of GnRH release in basal conditions and in the presence of veratridine. A significant inhibition (P less than 0.05) was observed using buserelin concentrations greater than 0.01 nM, whereas two GnRH analogs without biopotency (Leu8-GnRH, Des-gly10-N picolylamide GnRH, 100 nM) did not affect GnRH release. The two agonists of GnRH reduced by 43% to 66% (P less than 0.05) the occurrence of significant GnRH pulses. We conclude that, in vitro, the hypothalamic neuronal circuitry resulting in GnRH pulsatile secretion is dependent on calcium and glucose availability and is sensitive to an ultrashort-loop inhibitory feedback mechanism.
D000818:Animals; D002064:Buserelin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D004533:Egtazic Acid / Q000494:pharmacology; D005711:Gallopamil / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010507:Periodicity; D051381:Rats; D011919:Rats, Inbred Strains; D017329:Triptorelin Pamoate / Q000031:analogs & derivatives*; D014701:Veratridine / Q000494:pharmacology
D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; D005711:Gallopamil; D004533:Egtazic Acid; C019176:Tryptal; D014701:Veratridine; D005947:Glucose; D002064:Buserelin; D002118:Calcium