Abstract

Pituitary gonadotrophs express non-desensitizing gonadotropin-releasing hormone (GnRH) receptors and their activations leads to inositol 1,4,5-trisphosphate (InsP 3)-dependent Ca 2+ mobilization. When added in physiological concentration range GnRH induces baseline Ca 2+ oscillations, whereas in higher concentrations it induces a prolonged spike response accompanied with non-oscillatory or oscillatory plateau response. Here, we studied the recovery of calcium signaling during repetitive stimulation with short (10–30 s) GnRH pulses and variable interpulse intervals in neonatal gonadotrophs perfused with Ca 2+/Na +-containing, Ca 2+-deficient/Na +-containing, and Ca 2+-containing/Na +-deficient media. In Ca 2+/Na +-containing medium, baseline Ca 2+ oscillations recovered without refractory period and with a time constant of ∼20 s, whereas the recovery of spike response occurred after 25–35 s refractory period and with a time constant of ∼30 s. During repetitive GnRH stimulation, removal of Ca 2+ had only a minor effect on baseline oscillations but abolished spike response, whereas removal of Na + slightly extended duration of baseline oscillations and considerably prolonged spike response. These results indicate that two calcium handling mechanisms are operative in gonadotrophs: redistribution of calcium within InsP 3-sensitive and -insensitive pools and a sodium-dependent calcium efflux followed by calcium influx. Redistribution of Ca 2+ within the cell leads to rapid recovery of InsP 3-dependent pool, whereas the Na +-dependent Ca 2+ efflux pathway is activated by spike response and limits the time of exposure to elevated cytosolic Ca 2+ concentrations.

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