Lactoferrin gene expression is estrogen responsive in human and rhesus monkey endometrium

• Published in: Molecular human reproduction 2002-01, Vol.8 (1), p.58-67
• Main Authors: Teng, Christina T., Gladwell, Wesley, Beard, Clara, Walmer, David, Teng, Ching S., Brenner, Robert
• Format: Article
• Language: English
• Subjects: Adult; Aged; Animals; endometrium; Endometrium - cytology; Endometrium - metabolism; Estrogen Receptor alpha; estrogen response element; Estrogens - physiology; Female; Gene Expression Regulation; human and monkey; Humans; lactoferrin; Lactoferrin - genetics; Lactoferrin - metabolism; lactoferrin gene promoter; Macaca mulatta; Macaca mulatta - physiology; Male; Menstrual Cycle - physiology; Middle Aged; Milk - chemistry; Ovariectomy; Primates; Promoter Regions, Genetic; Prostate - drug effects; Prostate - metabolism; Receptors, Estrogen - metabolism; Response Elements; Steroidogenic Factor 1
• ISSN: 1360-9947; 1460-2407; 1460-2407
• DOI: 10.1093/molehr/8.1.58

We have previously shown that the estrogen responsiveness of the human lactoferrin gene in a transient transfection system is mediated through an imperfect estrogen response element (ERE) and a steroidogenic factor 1 binding element (SFRE) 26 bp upstream from ERE. Reporter constructs containing SFRE and ERE respond to estrogen stimulation in a dose-dependent manner, whereas mutations at either one of the response elements severely impaired the estrogen responsiveness. In this study, we demonstrated that estrogen receptor (ERα) binds to the human lactoferrin gene ERE and forms two complexes in an electrophoresis mobility shift assay (EMSA). These complexes could be supershifted by an antibody to ERα. We also showed that in normal cycling women, lactoferrin gene expression in the endometrium increases during the proliferative phase and diminishes during the luteal phase. This in-vivo study thus supported the finding from transient transfection experiments that the human lactoferrin gene expression is elevated in an environment with a high level of estrogen. The estrogen effect on lactoferrin gene expression in the rhesus monkey endometrium was studied by Western blotting and immunohistochemistry. The immunohistochemistry results showed that immunoreactive lactoferrin protein was not detectable in the untreated ovariectomized monkey endometrium, was elevated by estrogen treatment, and was suppressed by sequential, combined estrogen plus progesterone treatment. In conclusion, this study has shown that lactoferrin gene expression is responsive to estrogen in primate endometrium.