Functions and physiological roles of two types of estrogen receptors, ERα and ERβ, identified by estrogen receptor knockout mouse

Abstract

Estrogens, a class of steroid hormones, regulate the growth, development, and physiology of the human reproductive system. Estrogens also involve in the neuroendocrine, skeletal, adipogenesis, and cardiovascular systems. Estrogen signaling pathways are selectively stimulated or inhibited depending on a balance between the activities of estrogen receptor (ER) α or ERβ in target organs. ERs belong to the steroid hormone superfamily of nuclear receptors, which act as transcription factors after binding to estrogen. The gene expression regulation by ERs is to modulate biological activities, such as reproductive organ development, bone modeling, cardiovascular system functioning, metabolism, and behavior in both females and males. Understanding of the general physiological roles of ERs has been gained when estrogen levels were ablated by ovariectomy and then replenished by treatment with exogenous estrogen. This technique is not sufficient to fully determine the exact function of estrogen signaling in general processes in living tissues. However, a transgenic mouse model has been useful to study gene-specific functions. ERα and ERβ have different biological functions, and knockout and transgenic animal models have distinct phenotypes. Analysis of ERα and ERβ function using knockout mouse models has identified the roles of estrogen signaling in general physiologic processes. Although transgenic mouse models do not always produce consistent results, they are the useful for studying the functions of these genes under specific pathological conditions.

The immunoexpression of androgen receptor, estrogen receptors alpha and beta, vanilloid type 1 receptor and cytochrome p450 aromatase in rats testis chronically treated with letrozole, an aromatase inhibitor

“…Estrogens exert their cellular effect via estrogen receptors scattered throughout whole male reproductive tract. It was reported that estrogen signaling is depended upon a balance between ERa and ERb activities [11]. In this way, decreased estradiol level can affect expression of estrogen receptors.…”

“…The aromatase transcript was detected in pachytene and late spermatocytes, spermatids [9] and spermatozoa [10]. Androgens and estrogens exert their cellular effects via steroid receptors (ARs and ERs, respectively) of the nuclear receptor superfamily and act as ligand-dependent transcription factors [11]. After the binding of androgens, ARs undergo a conformational change, dimerization, translocation to the cell nucleus and binding to specific DNA sequence, thus modulating expression of target genes [12].…”

“…In ER-deficient mice and aromatase-deficient mice the abnormalities in the morphology of the seminiferous epithelium and spermatogenesis were found [11,23,24]. Thus, estrogens play crucial role for male fertility [25].…”

Impaired expression of testicular androgen receptor and collagen fibers in the testis of diabetic rats under HAART: the role of Hypoxis hemerocallidea

“…Many studies have proved that not only androgens have important functions in the adult male reproductive organ, but also estrogen and its receptors are essential for normal fertility in the male. Androgen and estrogen exert their cellular effects via steroid receptors (ARs and ERs, respectively) of the nuclear receptor superfamily and act as ligand-dependent transcription factors [26]. After the binding of androgens, ARs undergo a conformational change, dimerization, translocation to the cell nucleus and binding to specific DNA sequence, thus modulating expression of target genes [27].…”

Carcinogenesis and Sex Hormones: A Review

“…These hormonal fluctuations clearly indicated towards a disruption in the pituitary-adrenal-testicular axis. Thereof, it is suggested that these hormones might play a crucial role in the development and progression of oral cancer [26].…”