Estrogens, acting via the ER, are important regulators of the growth, differentiation, and function of many reproductive tissues including the uterus, vagina, ovary, mammary gland, and brain. The ability of estrogens to stimulate cell proliferation is well established and can be characterized experimentally by increases in DNA synthesis, as well as by changes in cell morphology.
In the uterus and mammary gland, estrogen-induced proliferation is accompanied by increased mRNA and protein expression of polypeptide growth factors (epidermal growth factor [EGF], transforming growth factor a [TGFa], and insulin-like growth factor-1 [IGF-I]) and their receptors, and it has been suggested that these growth factors may act as autocrine and/or paracrine mediators of estrogen action. buy asthma inhaler
A role for growth factor signaling in the estrogenic regulation of uterine biology was demonstrated in a series of experiments done by Korach and McLachlan. Administration of EGF antibodies to ovariectomized mice 3 days before hormone treatment significantly reduced the ability of estradiol to induce DNA synthesis and suggested that EGF may mediate, in part, the proliferative effects of this steroid ligand. When EGF was administered via slow-release pellets implanted under the kidney capsule, uterine and vaginal epithelial cell proliferation was stimulated, further supporting the hypothesis that EGF could mimic estrogen-like proliferative responses. These experiments were done in hypophysectomized, adrenalectomized, and ovariectomized mice, indicating that neither ovarian, adrenal, or pituitary hormones were required to stimulate cell proliferation in EGF-treated animals.