BIPHASIC REGULATION OF THE GONADOTROPIN-RELEASING HORMONE RECEPTOR BY RECEPTOR MICROAGGREGATION AND INTRACELLULAR CA2+ LEVELS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 25  (1) , 51-55
Abstract
Ca2+ is evidently both necessary and sufficient to evoke homologous up-regulation of the gonadotropin-releasing hormone (GnRH) receptor [rat pituitary]. Extracellular Ca2+ as well as RNA and protein synthesis were required for this event, and it was blocked by Ca2+ channel blockers. Drugs [A23187 (calcimycin) and veratridine] which stimulated increased intracellular Ca2+ levels also stimulated receptor up-regulation and enhanced responsiveness even in the absence of added GnRH. Such drugs were effective below the concentrations needed to evoke luteinizing hormone (LH) release, suggesting that enhanced levels of Ca2+, rather than LH [luteinizing hormone] depletion, is the responsible agent. A GnRH antagonist did not evoke up- or down-regulation; however, a conjugate of this antagonist, which stimulated microaggregation of the GnRH receptor, also stimulated these biphasic actions. Down-regulation of the GnRH receptor appears to be Ca2+-independent and does not require RNA or protein synthesis. Microaggregation of the GnRH receptor is apparently the final step in common to a branched pathway consisting of Ca2+-dependent (LH release, enhanced sensitivity and up-regulation) and Ca2+-independent (desensitization and down-regulation) events.