GNRH Secretion from GT1-7 Cells is Independently Suppressed by Uremic Milieu and Acidosis. 59

Background: Previous experiments suggest a central nervous alteration underlying the disturbed pubertal development observed in patients with chronic renal failure. We investigated whether substances present in uremic serum including metabolic acidosis have a direct inhibitory effect on GnRH-producing neurons. Subject: GnRH-producing cell line of neural origin (GT1-7).Interventions: Cells were incubated with 12.5% of uremic and nonuremic rat serum. Acidosis was achieved by stepwise reduction of HCO₃^- concentration from 25 to 15 mM. GnRH measured after 1 h and 24 h by RIA in the extracellular medium and in cell lysates. Results: Uremic serum caused a reduction of extracellular GnRH concentration by 40% and 30% after 1h and 24h, respectively, without changeing intracellular GnRH content. Reduced HCO₃^- resulted in a dose-dependent reduction of extracellular GnRH concentration by up to 35% after 1 h and 24 h. Conclusions: Our results indicate that uremic serum contains factor(s) able to suppress the secretion of GnRH from GT1-7 cells. Since normal pH and HCO₃^- concentrations were preserved during incubation with uremic serum, both the uremic and the acidotic state appear to inhibit GnRH secretion from GT1-7 cells independently.