GnRH agonist and GnRH antagonist protocols in ovarian stimulation: differential regulation pathway of aromatase expression in human granulosa cells

被引:16
作者
Khalaf, Mohamad [1 ,2 ]
Mittre, Herve [1 ,2 ,4 ]
Levallet, Jerome [1 ,2 ]
Hanoux, Vincent [1 ,2 ]
Denoual, Christine [3 ]
Herlicoviez, Michel [3 ]
Bonnamy, Pierre-Jacques [1 ,2 ]
Benhaim, Annie [1 ,2 ,3 ]
机构
[1] Univ Caen Basse Normandie, EA 2608, F-14032 Caen, France
[2] USC 2006, INRA, F-14032 Caen, France
[3] CHU Caen, Lab Fecondat Vitro, Serv Gynecol Obstet, F-14033 Caen, France
[4] CHU Caen, Genet Mol Lab, F-14033 Caen, France
关键词
GnRH agonist; GnRH antagonist; human granulosa cells; protein kinase C; aromatase; GONADOTROPIN-RELEASING-HORMONE; IN-VITRO FERTILIZATION; RIBONUCLEIC-ACID LEVELS; PREOVULATORY FOLLICLES; EXTRAPITUITARY ACTIONS; PROGESTERONE-RECEPTOR; GENE-EXPRESSION; PROTEIN-KINASE; GROWTH-FACTOR; LUTEAL CELLS;
D O I
10.1016/j.rbmo.2010.03.017
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
Gonadotrophin-releasing hormone (GnRH) agonists and antagonists have been widely used to prevent premature LH surge during ovarian stimulation. However, studies have shown a significantly lower serum oestradiol concentration on the day of human chorionic gonadotrophin administration for cycles using GnRH antagonist. This study compared aromatase gene expression in granulosa lutein cells from 50 women randomly assigned to receive either GnRH agonist (group 1, n = 28) or GnRH antagonist (group 2, n = 22). The cellular mechanism involved in the observed effects was also investigated. GnRH antagonist treatment significantly affected serum oestradiol concentration (1894 +/- 138 versus 1074 +/- 63 pg/ml; P <= 0.001), follicular-fluid oestradiol concentration in large follicles (18,565 +/- 2467 versus 10,184 +/- 1993 pg/ml; P <= 0.05), aromatase activity (9600 +/- 1179 versus 5376 +/- 997 fmol/10(6) cells/h; P <= 0.05) and mRNA aromatase/mRNA glyceraldehyde 3-phosphate dehydrogenase (15 +/- 3 versus 6 1; P < 0.05). Protein kinase C (PKC) activity in granulosa lutein cells from the GnRH antagonist group was 2.5-fold higher than in the GnRH agonist group. In-vitro experiments showed that selective down-regulation of PKC was only observed in GnRH-desensitized granulosa lutein cells. This report suggests that, in granulosa lutein cells, the modulation of the FSH-induced protein kinase A pathway by PKC was different in agonist versus antagonist cycles. (C) 2010, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:56 / 65
页数:10
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