Estrogen Receptor Function: Impact on the Human Endometrium

Abstract

The physiological role of estrogen in the female endometrium is well established. On the basis of responses to steroid hormones (progesterone, androgen, and estrogen), the endometrium is considered to have proliferative and secretory phases. Estrogen can act in the endometrium by interacting with estrogen receptors (ERs) to induce mucosal proliferation during the proliferative phase and progesterone receptor (PR) synthesis, which prepare the endometrium for the secretory phase. Mouse knockout studies have shown that ER expression, including ERα, ERβ, and G-protein-coupled estrogen receptor (GPER) in the endometrium is critical for normal menstrual cycles and subsequent pregnancy. Incorrect expression of ERs can produce many diseases that can cause endometriosis, endometrial hyperplasia (EH), and endometrial cancer (EC), which affect numerous women of reproductive age. ERα promotes uterine cell proliferation and is strongly associated with an increased risk of EC, while ERβ has the opposite effects on ERα function. GPER is highly expressed in abnormal EH, but its expression in EC patients is paradoxical. Effective treatments for endometrium-related diseases depend on understanding the physiological function of ERs; however, much less is known about the signaling pathways through which ERs functions in the normal endometrium or in endometrial diseases. Given the important roles of ERs in the endometrium, we reviewed the published literature to elaborate the regulatory role of estrogen and its nuclear and membrane-associated receptors in maintaining the function of endometrium and to provide references for protecting female reproduction. Additionally, the role of drugs such as tamoxifen, raloxifene, fulvestrant and G-15 in the endometrium are also described. Future studies should focus on evaluating new therapeutic strategies that precisely target specific ERs and their related growth factor signaling pathways.

The Hepatoprotective and Hepatotoxic Roles of Sex and Sex-Related Hormones

“…Estradiol is the most important form of estrogen, responsible for the regulation of female characteristics, the maturation of accessory sex organs, the menstruation-ovulation cycle, and the production of the mammary duct system ( 50 ). Serum concentrations of estrogens such as estradiol vary periodically throughout the menstrual cycle, with estradiol being the most abundant estrogen in females of childbearing age, except in the early follicular phase ( 51 ).…”

Resveratrol Analogues as Selective Estrogen Signaling Pathway Modulators: Structure–Activity Relationship

“…It may also be indicated that ERα and ERβ regulate processes connected with the female reproductive system in regulating several other physiological and pathophysiological processes in the human body. Disrupted ER signaling leads to the development of different diseases, such as osteoporosis, neurodegeneration, inflammation and metabolic and cardiovascular diseases [ 19 ]; however, the most important indications to modify their activity connected with estrogen-related cancers such as breast [ 19 ], endometrial [ 20 ], cervical [ 21 ] and ovarian cancer [ 22 ].…”

“…The role of ERβ and its variants in cancerogenesis, breast cancer progression and prognosis response to therapy is even more complex and not fully understood despite it being over 25 years since its discovery. It seems evident that understanding is crucial for the further design of diagnostic and therapeutic strategies not only for breast and endometrial cancer [ 20 , 23 ]. Although we know relatively the most about the effect of ERβ on these cancers, the situation seems much more complicated than in the case of ERα.…”

Estradiol mediates the interaction of LINC01541 and miR-429 to promote angiogenesis of G1/G2 endometrioid adenocarcinoma in-vitro: A pilot study

“…In vivo study has shown that ER including ESR1, ESR2 and G protein-coupled estrogen receptor (GPER) is essential for a normal menstrual cycle. Incorrect expression of ERs can cause EC, ESR1 promotes uterine cell proliferation and increased the risk of EC, while ESR2 has the opposite effects (22). Other research has shown that LINC01541 inhibits VEGFA expression in endometrial stromal cells and that E2 stimulation significantly inhibits the expression of LINC01541, whereas overexpression of LINC01541 attenuates the migration and invasion of endometrial stromal cells induced by E2 (8).…”