A pulsatile GnRH signal is required for the maintenance of LH and FSH secretion. Studies in animals and in perifused pituitary cells have shown that continuous exposure to GnRH leads to decreased gonadotropin secretion and a blunted secretory response to subsequent pulses of GnRH, a process referred to as homologous desensitization. In the current study, we demonstrate that the duration of continuous GnRH exposure required to desensitize the gonadotrope in vitro is less than the durations of most in vivo GnRH pulses. Perifused male rat pituitary cells were tested with 20-sec pulses of 100 nM GnRH at 5-min intervals before, immediately upon termination of, and after GnRH infusions of varying concentration and duration. Desensitization in response to a GnRH infusion was calculated as the decrease in the LH response to the pulse of GnRH immediately after the infusion (Dsn pulse) compared to the mean LH response to GnRH pulses before and after the infusion. Gonadotropes were completely desensitized after a 2-min infusion of 10 nM GnRH (P > 0.05), the shortest duration tested. Endogenous GnRH pulses, by contrast, average more than 5 min in length. When the duration of GnRH infusion was held constant at 4 min, a concentration response for GnRH-induced desensitization was observed. Gonadotropes were desensitized by GnRH concentrations as low as 1 nM (P < 0.05), and maximal desensitization was observed with 5 nM GnRH. To determine the recovery period for GnRH-induced desensitization, a second series of experiments was performed. Experiments were conducted as described above, except the cells were perifused with medium that did not contain GnRH (recovery) for varying periods between the GnRH infusion and the Dsn pulse. A small response (16% of control) to the Dsn pulse of GnRH was observed after 1 min of recovery, and the response was not different from the control value (P > 0.05) after a 3-min recovery period. This recovery period is consistent with the ability to respond to endogenous GnRH pulses, which rarely exceed two per h. We conclude that GnRH-induced secretory desensitization and recovery occur within endogenous GnRH pulse durations and interpulse intervals, respectively. These data raise the possibility that homologous desensitization occurs under some in vivo conditions, providing an unexpected mechanism for physiological regulation of gonadotropin secretion.
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