Activation of the insulin-like growth factor binding protein-1 promoter byprogesterone receptor in decidualized human endometrial stromal cells

Insulin-like growth factor binding protein-1 (IGFBP-1) is induced extensive ly when human endometrial stromal cells are decidualized by progestin and r elaxin in a long-term primary culture system. The purpose of this study is to investigate whether progesterone receptor (PR) directly activates the IG FBP-1 gene promoter. In decidualized stromal cells, activity of the IGFBP-1 promoter (from -1.2 kb to +68 bp) containing putative progesterone-respons e elements (PREs) was increased 80-fold. Mutation of either 5' or 3' half-s ite of the putative PRE1 site (from - 193 to - 179 bp) reduced the promoter activity. Mutations that converted PRE1 closer to consensus PRE increased the promoter activity. In undifferentiated stromal cells, mutations of PRE sites had no effect on the promoter activity. When a PR expression vector ( hPR1) was cotransfected, progestin increased promoter activity derived from p275CAT but not from p1.2CAT, suggesting that the function of PRE1 was rep ressed by the region from - 1.2 kb to - 275 bp in the promoter. Progestin d id not increase promoter activity derived from p275CAT without cotransfecti on of hPR1, suggesting that endogenous PR alone is insufficient to activate PRE1. In summary, results indicate that the PRE1 site of the IGFBP-1 promo ter mediates a direct activation of PR on transcription specifically in dec idualized stromal cells. (C) 1999 Elsevier Science Ireland Ltd. Ail rights reserved.