Gonadotropin-Releasing Hormone-I-Mediated Activation of Progesterone Receptor Contributes to Gonadotropin α-Subunit Expression in Mouse Gonadotrophs

Abstract

In pituitary cells, cross talk between GnRH-I and the progesterone receptor accentuates gonadotropin production. We show that GnRH-I activates a progesterone response element (PRE)-driven luciferase reporter gene at 8 h and gonadotropin α-subunit (gsuα) gene expression at 24 h in two mouse gonadotrope cell lines, αT3-1 and LβT2. In αT3-1 cells, progesterone had an additive effect on GnRH-I-induced PRE-luciferase reporter gene activity but not on GSUα mRNA levels. However, progesterone had no synergistic effect on the GnRH-I-induced expression of these genes in LβT2 cells. Up-regulation of the PRE-luciferase reporter gene by GnRH-I was attenuated by pretreatment with protein kinase A (H89) and protein kinase C (GF109203X) inhibitors in both cell lines, whereas only GF109203X inhibited GnRH-I-induced GSUα mRNA levels. Most important, in both cell lines within the same time frame, knockdown of progesterone receptor levels by small interfering RNA reduced GnRH-I activation of GSUα mRNA levels by approximately 40%. We conclude that the effect of GnRH-I on gsuα expression in both αT3-1 and LβT2 cells is mediated by ligand-independent activation of progesterone receptor and that this contributes to the self-priming effect of GnRH-I in the pituitary.