Activation of the human IGFBP-1 gene promoter by progestin and relaxin in primary culture of human endometrial stromal cells

Mol Cell Endocrinol. 1994 Aug;104(1):39-46. doi: 10.1016/0303-7207(94)90049-3.


We have studied the activity for the insulin-like growth factor binding protein-1 (IGFBP-1) gene promoter in human endometrial stromal cells by transient transfection. The promoter activity derived from p3.6CAT or p3.6Luc (3400 bp IGFBP-1 promoter 5' to the reporter gene chloramphenicol acetyltransferase or luciferase) was minimal in unstimulated cells. A time study over 13 days of culture showed that the promoter activity increased exponentially to > 10(4) fold in cells treated with medroxyprogesterone acetate (MPA) and relaxin (RLX). Induction of the IGFBP-1 gene promoter activity by hormones was similar to the secretion pattern of IGFBP-1 in endometrial stromal cells. MPA alone caused a moderate induction, 3-40-fold increase over the control. Deletion analysis showed that two regions in the IGFBP-1 gene promoter were responsible for the activation of the IGFBP-1 gene. The basal promoter region, termed bp1-A (+68 bp to -1.205 kb), contains multiple sections of regulatory sequence including a cis-element CCAAT (-72 bp). A DNase I protection assay in the bp-1A region revealed four distinct binding regions, one of which contained the CCAAT box region. Another promoter region, termed bp1-B (-2.6 to -3.4 kb), mediated 95% of the total promoter activity in endometrial stromal cells. The bp1-B region also contains multiple regulatory sequences. Mutation and DNase I protection assay suggest that Sp1-like binding site at -2.63 kb was a regulatory site responsible for the activation of IGFBP-1 gene promoter.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Base Sequence
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cells, Cultured
  • Endometrium / cytology*
  • Endometrium / drug effects
  • Endometrium / metabolism
  • Female
  • Gene Deletion
  • Gene Expression Regulation / drug effects
  • Humans
  • Insulin-Like Growth Factor Binding Protein 1
  • Medroxyprogesterone Acetate / pharmacology
  • Middle Aged
  • Molecular Sequence Data
  • Mutation
  • Progestins / pharmacology*
  • Promoter Regions, Genetic / genetics*
  • Relaxin / pharmacology*
  • Time Factors
  • Transfection


  • Carrier Proteins
  • Insulin-Like Growth Factor Binding Protein 1
  • Progestins
  • Relaxin
  • Medroxyprogesterone Acetate