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Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden (K.D.-W., J.-A.G.); Institut National de la Santé et de la Recherche Médicale U540, Endocrinologie Moléculaire et Cellulaire des Cancers, Montpellier, France (V.C.); Baylor College of Medicine, Houston, Texas (S.A.F.); Fox Chase Cancer Center, Philadelphia, Pennsylvania(More)
All scientific investigations begin with distinct objectives: first is the hypothesis upon which studies are undertaken to disprove, and second is the overall aim of obtaining further information, from which future and more precise hypotheses may be drawn. Studies focusing on the generation and use of gene-targeted animal models also apply these goals and(More)
Estrogens influence the differentiation and maintenance of reproductive tissues and affect lipid metabolism and bone remodeling. Two estrogen receptors (ERs) have been identified to date, ERalpha and ERbeta. We previously generated and studied knockout mice lacking estrogen receptor alpha and reported severe reproductive and behavioral phenotypes including(More)
Oestrogen is considered to be the 'female' hormone, whereas testosterone is considered the 'male' hormone. However, both hormones are present in both sexes. Thus sexual distinctions are not qualitative differences, but rather result from quantitative divergence in hormone concentrations and differential expressions of steroid hormone receptors. In males,(More)
The steroid hormone 17β-estradiol (E 2) is a key regulator of growth, differentiation and function in a wide array of target tissues, including the male and female reproductive tracts, mammary gland, skeletal and cardiovascular systems. The predominant biological effects of E 2 are mediated through two distinct intracellular receptors, ERα and ERβ, each(More)
The physiological responses of the rodent uterus to acute estrogen (E) dosing can be divided into early and late events. Examples of early responses include increased RNA transcription, hyperemia, and water imbibition 2 and 6 h following E administration respectively, whereas later responses include cycles of DNA synthesis and mitosis of epithelial cells(More)
Estrogen receptor and its ligand, estradiol, have long been thought to be essential for survival, fertility, and female sexual differentiation and development. Consistent with this proposed crucial role, no human estrogen receptor gene mutations are known, unlike the androgen receptor, where many loss of function mutations have been found. We have generated(More)
Estrogens stimulate the in vivo proliferation of epithelial cells of the mouse uterus. The cumulative evidence from several earlier studies suggests that the mitogenic effect of estrogens is mediated indirectly through a polypeptide growth factor. The primary focus of the present investigation was to determine whether an epidermal growth factor(More)
The reproductive system of male mice homozygous for a mutation in the estrogen receptor (ER) gene (ER knock-out; ERKO) appears normal at the anatomical level. However, these males are infertile, indicating an essential role for ER-mediated processes in the regulation of male reproduction. Adult ERKO male mice have significantly fewer epididymal sperm than(More)
Mice lacking estrogen receptors alpha and beta were generated to clarify the roles of each receptor in the physiology of estrogen target tissues. Both sexes of alphabeta estrogen receptor knockout (alphabetaERKO) mutants exhibit normal reproductive tract development but are infertile. Ovaries of adult alphabetaERKO females exhibit follicle(More)