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Review
. 2014 Mar;14(1):3-8.
doi: 10.1016/j.repbio.2013.12.002. Epub 2013 Dec 21.

Estrogen hormone physiology: reproductive findings from estrogen receptor mutant mice

Katherine J Hamilton  1 , Yukitomo Arao  1 , Kenneth S Korach  2
Affiliations
Review

Estrogen hormone physiology: reproductive findings from estrogen receptor mutant mice

Katherine J Hamilton et al. Reprod Biol. 2014 Mar.

Abstract

Estrogen receptors (ERs) play a crucial role in reproduction and normal physiology. The two sub-types of ER (ERα and β) are expressed in various levels in different tissues and selective cell types. Gene targeting technology allowed us to produce lines of mice with disrupted ERα (αERKO) and ERβ genes (βERKO) as well as a compound αβERKO in the whole body. Male and female αERKO mice are infertile. Estrogen, EGF and IGF-1 treatments failed to induce uterine growth and DNA synthesis in αERKO uteri. αERKO females are infertile due to hypoplastic uteri and hyperemic ovaries with no corpora lutea due to persistent LH stimulation from loss of negative feedback. αERKO males are infertile, with testicular atrophy and seminiferous tubule dysmorphogenesis producing decreased spermatogenesis and inactive sperm. βERKO females show arrested folliculogenesis and subfertility. Ovarian analyses indicate differential gene expression related to ovulatory stimulation deficits including lack of LH, PR, Cyp19 and Cox2 expression. A unique ovarian phenotype is found only in αβERKO females showing transdifferentiation of granulosa cells to Sertoli cells. We describe here several novel mouse models which possess ERα gene modification. To understand ERα function in uterine endometrial epithelial cells, we generated a tissue selective ERα gene disrupted mouse model, the uterine epithelial-specific ERα knockout (UtEpiαERKO). To understand the physiological role of ERα functional domains, we generated a mouse model with a mutation in the ligand dependent transcription activation domain of ERα (AF2ERKI). Findings from the ERα mutant mice suggest that the absence of functional ERα is not lethal and results in significant endocrine effects and altered physiological processes.

Keywords: Estrogen receptor; Fertility; Genetically modified mouse; Ovary; Transactivation function; Uterus.

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References

    1. Burns KA, Korach KS. Estrogen receptors and human disease: an update. Arch Toxicol. 2012;86(10):1491–504. epub 01.06.12. - PMC - PubMed
    1. Deroo BJ, Korach KS. Estrogen receptors and human disease. J Clin Invest. 2006;116(3):561–70. epub 03.03.06. - PMC - PubMed
    1. Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K, et al. The nuclear receptor superfamily: the second decade. Cell. 1995;83(6):835–9. epub 15.12.95. - PMC - PubMed
    1. Couse JF, Lindzey J, Grandien K, Gustafsson JA, Korach KS. Tissue distribution and quantitative analysis of estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta) messenger ribonucleic acid in the wild-type and ERalpha-knockout mouse. Endocrinology. 1997;138(11):4613–21. - PubMed
    1. Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K, et al. The nuclear receptor superfamily: the second decade. Cell. 1995;83(6):835–9. - PMC - PubMed

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