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

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/106 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.