Endocrine Journal
Online ISSN : 1348-4540
Print ISSN : 0918-8959
ISSN-L : 0918-8959
ORIGINALS
GnRH Antagonist-induced Down-regulation of the mRNA Expression of Pituitary Receptors: Comparisons with GnRH Agonist Effects
Mariko MURASETsuguo UEMURAMengge GAOMae INADAToshiya FUNABASHIFumiki HIRAHARA
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2005 Volume 52 Issue 1 Pages 131-137

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Abstract

In order to compare the mechanism for the down regulation of the mRNA expression of pituitary receptors induced by GnRH antagonist (GnRHant) to that by GnRH agonist (GnRHa), we examined the effects of GnRHant (Cetrorelix, 333 μg/kg/day), GnRHa (leuprolide depot, 333 μg/kg), and GnRHant combined with GnRHa on LH response to exogenous GnRH, pituitary LH content, LHβ subunit mRNA, and GnRH receptor (GnRH-R) mRNA levels at 2, 5, 24, 72 hours, and 7 days after the treatment in ovariectomized rats. GnRHant significantly decreased serum LH, the LH response of the pituitary to exogenous GnRH, and the pituitary LH content compared to the control treatment, though GnRHa significantly increased serum LH. GnRHant with GnRHa significantly diminished the GnRHa-induced flare-up phenomenon. GnRHant significantly decreased LHβ mRNA and GnRH-R mRNA levels, but the magnitude of the decrease in these mRNA levels by GnRHant was significantly less than those by GnRHa until 72 hours following treatment. Prolonged treatment of GnRHant caused a marked inhibition of LHβ mRNA and GnRH-R mRNA expression, similar to that caused by GnRHa. Combination treatment with GnRHa and GnRHant was demonstrated to decrease LHβ mRNA and GnRH-R mRNA levels as much as GnRHa alone and GnRHant alone over 7 days of the treatment. The present study showed differences between GnRHant and GnRHa treatment in the reduction of GnRH-R mRNA levels up to 72 hours after the treatment, and indicated that the suppression of GnRH-R mRNA by GnRHant was the maximal by GnRHa 7 days after the treatment because more profound suppression was not observed upon additional treatment with GnRHa. The findings in the present study support the hypothesis that the mechanism by which GnRHant leads to down-regulation of the mRNA expression of pituitary receptors is similar to that of GnRHa.

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© The Japan Endocrine Society
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