Mechanism of estrogen action : Lessons from the estrogen receptor-α knockout mouse

• Published in: Biology of reproduction Vol. 59; no. 3; pp. 470 - 475
• Main Authors: COOKE, P. S, BUCHANAN, D. L, LUBAHN, D. B, CUNHA, G. R
• Format: Conference Proceeding Journal Article
• Language: English
• Published: Madison, WI Society for the Study of Reproduction 01-09-1998
• Subjects: Animals; Biological and medical sciences; Breast - cytology; Cell Differentiation; Cell Division - drug effects; Epithelial Cells - cytology; Epithelial Cells - physiology; Estradiol - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Hormone metabolism and regulation; Mammalian female genital system; Mice; Mice, Knockout; Receptors, Estrogen - genetics; Receptors, Estrogen - physiology; Stromal Cells - metabolism; Uterus - cytology; Vagina - cytology; Vertebrates: reproduction; Estrogen; Rodentia; 17β-Estradiol; Vagina; Review; Epithelium; Ovarian hormone; Vertebrata; Mammalia; Mouse; Uterus; Female genital system; Hormonal regulation; Stromal cell; Sex steroid hormone; Mechanism of action; Hormonal receptor
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod59.3.470

Estradiol-17 beta (E sub(2)) stimulates uterine and vaginal epithelial proliferation in vivo. E sub(2) also plays a critical role in other aspects of uterine and vaginal growth and adult function, and it is obligatory for normal epithelial morphogenesis, cytodifferentiation, and secretory activity in these organs. E sub(2) elicits its effects via the estrogen receptor (ER), which functions as a ligand-activated transcription factor to turn on target genes in E sub(2)-responsive tissues. In this review, we will summarize earlier findings suggesting that the mitogenic and possibly other important E sub(2) effects on uterine and vaginal epithelium could be mediated through stromal ER. We have recently developed a new experimental methodology that allows a more definitive analysis of the respective roles of stromal and epithelial ER alpha in E sub(2)-induced epithelial proliferation and a variety of other epithelial responses to E sub(2) in the vagina, uterus, and mammary gland. Our data clearly suggest that E sub(2)-induced epithelial mitogenesis is mediated indirectly by stromal ER alpha in female reproductive organs. These results will be presented here, along with a discussion of preliminary results related to the role of stromal and epithelial ER alpha in various other uterine and vaginal differentiative events.