Abstract
Although it is well recognized that continuous administration of gonadotropin-releasing hormone agonist (GnRHa) induces pituitary desensitization, the precise molecular mechanism of this phenomenon is still unclear. To test the hypothesis that pituitary gonadotroph desensitization is mediated by a change in GnRH receptor (GnRH-R) gene expression, the GnRH-R mRNA concentration was analyzed in immature female rats during GnRHa treatment. Northern blot hybridization was used to determine the GnRH-R mRNA concentration several times after an injection of TAP-144-SR, a slow releasing GnRHa. The GnRH-R mRNA readings were 92.7±9.5%, 49.9±5.0%, 35.7±2.3% and 73.8± 5.7% (Mean±SD) compared to each control value at 1, 2, 4 and 8 weeks, respectively, after a single injection of 0.94mg TAP-144 SR. These changes in GnRH-R mRNA coincided with the changes in gonadotropin secretion and LH-β mRNA in response to GnRH in the results of our previous report. The present results indicate that the reduction of the number of pituitary GnRH-R sites induced by continuous stimulation with GnRHa is regulated at a transcriptional level.
