CONTINUOUS STIMULATION OF GONADOTROPIN-RELEASING-HORMONE (GNRH) RECEPTORS BY GNRH AGONIST DECREASES PITUITARY GNRH RECEPTOR MESSENGER-RIBONUCLEIC-ACID CONCENTRATION IN IMMATURE FEMALE RATS

Although it is well recognized that continuous administration of gonad otropin-releasing hormone agonist (GnRHa) induces pituitary desensitiz ation, the precise molecular mechanism of this phenomenon is still unc lear. To test the hypothesis that pituitary gonadotroph desensitizatio n is mediated by a change in GnRH receptor (GnRH-R) gene expression, t he GnRH-R mRNA concentration was analyzed in immature female rats duri ng 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) co mpared to each control value at 1, 2, 4 and 8 weeks, respectively, aft er a single injection of 0.94 mg TAP-144 SR. These changes in GnRH-R m RNA coincided with the changes in gonadotropin secretion and LH-beta m RNA in response to GnRH in the results of our previous report. The pre sent results indicate that the reduction of the number of pituitary Gn RH-R sites induced by continuous stimulation with GnRHa is regulated a t a transcriptional level.