Desensitization to native molecular forms of gonadotropin-releasing hormone in the goldfish pituitary: Dependence on pulse frequency and concentration

Abstract

Homologous desensitization of gonadotropin-releasing hormone (GnRH) was investigated using goldfish pituitary fragments in vitro. The two native GnRH peptides, sGnRH ([Trp7, Leu8]-GnRH) and cGnRH-II ([His5, Trp7, Tyr8]-GnRH) were administered either continuously or in pulsatile fashion at different frequencies and concentrations. Continuous treatment (60 min) with either sGnRH or cGnRH-II at 10 −7, 10 −8, and 10 −9 M resulted in desensitization of goldfish pituitary in a biphasic fashion, characterized by an initial rapid peak of GTH release (phase 1), followed by a lower sustained release of GTH remaining at a stable concentration above the basal level (phase 2). Pituitary fragments were then washed for 60 min and further treated continuously (60 min) with the same concentrations of sGnRH or cGnRH-II (second treatment). Total sGnRH- or cGnRH-II-induced GTH release during the second treatment period was significantly lower than that observed during the initial treatment period, depending upon the concentration of the peptides. The second phase of GTH release was more pronounced at lower concentrations compared to that observed following 10 −7 M treatment, especially for sGnRH. Pulsatile treatment with either sGnRH or cGnRH-II (2-min pulses of 10 −7, 10 −8, and 10 −9 M given every 20 min) resulted in significant desensitization of the pituitary GTH release. Reduction of pulse frequency to 2 min treatment every 60 min resulted in a lower degree of desensitization; little or no desensitization was observed following treatment with 10 −8 and 10 −9 M cGnRH-II or 10 −9 M sGnRH. A further reduction in frequency to 2-min pulses of sGnRH or cGnRH-II (10 −7 or 10 −8 M) given every 90 min did not result in desensitization of the pituitary GTH release. In summary, the present study demonstrates that GnRH-induced desensitization is dependent on both pulse frequency and concentration in the goldfish pituitary. These findings support the hypothesis that pulsatile secretion of the native GnRH peptides may be essential for maintenance of normal pituitary GTH release in goldfish.