Estrogen Receptor-β in Women’s Health

Multifaceted roles of Estrogen Receptor-β

Key Points

Highlight:

• From the 1950s the initial identification of estrogen receptor (ER) has led to the findings of its roles in several cellular and physiological processes. In the 1990s, the discovery of estrogen receptor-β (ERβ) increasingly showed the multifaceted roles of ER biology.

Importance:

• ER expression patterns in tissues are diverse with some cells expressing either only ERα or ERβ or both. This adds to the complexity of understanding ERs functions in normal and diseases.

What's done here:

• The goal of this issue is to highlight the role of ERβ in physiological and pathological processes that are specific to women.

Data:

• ERα is a leading therapeutic treatment for breast cancer. The expression levels of ERβ in invasive breast cancer are reduced and signals potential differential functions of ERα and ERβ in breast cancer.
• The similarities and differences between ERα and ERβ can be exploited in terms of generating subtype-specific agonists to act in a gene-specific and tissue-selective way.
• In endometriosis, the higher ERβ expression in endometriotic stromal cells in comparison with endometrial stromal cells may suppress the endometriotic stromal cell ERα expression and contributes to progesterone resistance.
• In terms of ERβ roles in gonadotropin-releasing hormone (GnRH) neurons, it may regulate neuronal activity, gene expression, and pulsatile secretion of GnRH, which are key factors in ovulation and menstruation.

Lay Summary

Since the discovery of estrogen receptor (ER), there has been a vast number of studies regarding its functions in cellular and physiological processes. The identification of estrogen receptor-β (ERβ), a second receptor, resulted in a much more complex understanding of the ER biology. Because of the diverse ERs expression patterns, detailed understanding of their tissue-specific roles can be difficult to decipher. This article highlights the role of ERβ that is relevant to various physiological and pathological processes in women.

Breast cancer is a classic example where understanding ER biology is important since ERα is the leading target for pharmacological treatment. Although the role of ERβ remains elusive and could be the opposite because of its decreased expression levels in invasive breast cancer. Endometriosis is another example where ER biology is important. ERβ appears to play a predominant role in endometriosis pathogenesis and may contribute to progesterone resistance. Furthermore, ERβ may contribute to ovulation and menstruation regulation by affecting gonadotropin-releasing hormone (GnRH) through regulating neuronal activity, gene expression, and pulsatile secretion of GnRH.

These studies and reports demonstrate our emerging understanding on ERβ. Since unwanted side effects associated with estrogen-related therapies still exist, improved understanding of the similarities and differences between ERα and ERβ will close the gap to maximize future clinical practices for women’s health.