The mechanism by which GnRH stimulates annexin A5 expression was examined with LβT2 gonadotrope cells. Continuous stimulation with GnRH analog (GnRHa, Des-Gly10 [Pro9]-GnRH ethylamide) transiently elevated LHβ mRNA expression while maintaining annexin A5 mRNA at high levels for 24 h. GnRH antagonist blocked the effect of GnRHa on annexin A5. While 12-O-tetradecanoyl-phorbol-13 acetate, a protein kinase C activator, increased the expression of annexin A5 mRNA, bisindolylmaleimide, an inhibitor

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... protein kinase C, suppressed GnRHa-stimulated expression of annexin A5 and LHβ mRNA. GnRHa stimulation of LHβ mRNA was inhibited to a greater extent than annexin A5 by a calcium chelator BAPTA/AM. Although a calcium ionophore ionomycin stimulated the expression of both genes, only LHβ was down-regulated. The MAPK kinase inhibitor PD98059 inhibited GnRHa induction of annexin A5 but not LHβ mRNA. EGF stimulated the expression of annexin A5 mRNA but caused only a transient effect on LHβ mRNA expression. These results indicate that GnRH stimulation of signaling pathway for annexin A5 mRNA expression is distinct from that of LHβ mRNA and dependent more on MAPK.