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 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 0.94 mg TAP-144 SR. These changes in GnRH-R mRNA coincided with the changes in gonadotropin secretion and LH-beta 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.
Sakakibara
H
H
Department of Obstetrics and Gynecology, Yokohama City University School of Medicine, Japan.
Taga
M
M
Ikeda
M
M
Kurogi
K
K
Minaguchi
H
H
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D018076:DNA, Complementary / Q000032:analysis; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D016729:Leuprolide / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010903:Pituitary Gland, Anterior / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011966:Receptors, LHRH / Q000187:drug effects* / Q000235:genetics*
D018076:DNA, Complementary; D012333:RNA, Messenger; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D016729:Leuprolide