%0 Journal Article
%T Estrogen receptor transcription and transactivation: Estrogen receptor knockout mice - what their phenotypes reveal about mechanisms of estrogen action
%A Sylvia Curtis Hewitt
%A John F Couse
%A Kenneth S Korach
%J Breast Cancer Research
%D 2000
%I BioMed Central
%R 10.1186/bcr79
%X Estrogen has many roles in reproduction, and the generation of the estrogen receptor (ER)¦Á and ER¦Â knockout (¦ÁERKO and ¦ÂERKO) mice has further illustrated its roles and mechanisms. Interestingly, both sexes of the ¦ÁERKO mice are infertile, whereas only the ¦ÂERKO female has shown impaired fertility. In the male ¦ÁERKO mice, infertility is due to deficits at several points in the reproductive process, including severe reduction in sperm numbers and lack of sperm function, as well as abnormal sexual behavior. The seminiferous tubules of the ¦ÁERKO testes show progressive dilation that is accompanied by degeneration of the seminiferous epithelium (Fig. 1) [1*,2*]. Transplanted ¦ÁERKO sperm was functional when developed in normal host testes [3**]. In contrast, the testes of the ¦ÂERKO mice appear normal (Fig. 1), and produce sufficient and functional sperm to allow fertility, resulting in production of offspring in mice examined to date. Therefore, ER¦Á appears to be more critical than ER¦Â in mediation of the estrogen actions necessary for maintenance of healthy testicular structures and the somatic cell function required for successful sperm maturation.Normally, the female rodent reproductive tract grows and matures in response to cycling ovarian hormones, including estradiol. The growth and maturation of the epithelial portion and the preparation of the stromal layer is thought to be important for successful implantation and pregnancy to occur. The infertility of the female ¦ÁERKO mouse is due in part to the insensitivity of the uterus to the mitogenic and differentiative actions of estrogen [4**,5**] (Fig. 2). Microscopic evaluation of the ¦ÁERKO uterine tissue indicates that all expected tissues are present but appear immature, as illustrated by a reduced number of glands in the endometrium (Fig. 3). ER¦Á is thus not necessary for development of the uterus, but is necessary for complete maturation and function of the tissue. In contrast, the wild-type and ¦ÂERKO uteri are in
%K estrogen receptor
%K estrogen receptor knockout
%K transgenic
%U http://breast-cancer-research.com/content/2/5/345