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Lactoferrin gene expression is estrogen responsive in human and rhesus monkey endometrium
Christina T Teng1, Wesley Gladwell, Clara Beard
1Gene Regulation Group, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. TEng@niehs.nih.gov
Molecular Human Reproduction
|January 5, 2002
Summary
Estrogen regulates human lactoferrin gene expression in the endometrium. This study confirms estrogen receptor binding and demonstrates lactoferrin levels increase with estrogen in primates.
Area of Science:
- Endocrinology
- Molecular Biology
- Reproductive Science
Background:
- The human lactoferrin gene's estrogen responsiveness is mediated by an imperfect estrogen response element (ERE) and a steroidogenic factor 1 binding element (SFRE).
- Previous studies indicated dose-dependent responses to estrogen stimulation in reporter constructs containing both ERE and SFRE.
Purpose of the Study:
- To investigate the binding of estrogen receptor alpha (ERalpha) to the human lactoferrin gene ERE.
- To confirm the in vivo regulation of human lactoferrin gene expression by estrogen in the endometrium.
- To examine the effect of estrogen and progesterone on lactoferrin gene expression in primate endometrium.
Main Methods:
- Electrophoresis mobility shift assay (EMSA) to detect ERalpha binding to the ERE.
- Analysis of human endometrial lactoferrin gene expression during the menstrual cycle.
- Western blotting and immunohistochemistry in rhesus monkey endometrium.
Main Results:
- ERalpha binds to the human lactoferrin gene ERE, forming two complexes detectable by EMSA.
- Human lactoferrin gene expression is elevated during the proliferative phase (high estrogen) and diminished during the luteal phase.
- Estrogen treatment increased lactoferrin protein in monkey endometrium, while combined estrogen and progesterone suppressed it.
Conclusions:
- Estrogen receptor alpha directly binds to the human lactoferrin gene's regulatory elements.
- Lactoferrin gene expression is significantly influenced by the hormonal milieu, specifically estrogen levels, in the primate endometrium.
- These findings support the role of estrogen in regulating lactoferrin expression in vivo.