Roles of estrogen and its receptors in polycystic ovary syndrome

Abstract

Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by abnormal steroid hormone levels in peripheral blood and poor-quality oocytes. In the ovary, androgen is produced by theca cells, and estrogen is produced by granulosa cells. Androgen is converted to estrogen in granulosa cells, with cytochrome P450 aromatase as the limiting enzyme during this process. Estrogen receptors (ER) include ER alpha, ER beta, and membrane receptor GPR30. Studies have demonstrated that the abnormal functions of estrogen and its receptors and estradiol synthesis-related enzymes are closely related to PCOS. In recent years, some estrogen-related drugs have made significant progress in clinical application for subfertility with PCOS, such as letrozole and clomiphene. This article will elaborate on the recent advances in PCOS caused by abnormal expression of estrogen and its receptors and the application of related targeted small molecule drugs in clinical research and treatment.

Keywords: estrogen; estrogen receptor; estrogen signaling; ovary; polycystic ovary syndrome.

FIGURE 1

Schematic representation of estrogen biosynthesis. E1: estrone; E2:17β-estradiol; E3: Estriol; E4: Estetrol; Cyp: Cytochrome P450; HSD: Hydroxysteroid dehydrogenase; HEAS: Dehydroepiandrosterone sulfate; DHEA: Dehydroepiandrosterone; LH: Luteinizing hormone; FSH: Follicle stimulating hormone.

FIGURE 2

Different patterns of estrogen receptor signaling. (a) Classic ERE genomic pattern: The E2-ER complex acts as a transcriptional activator that promotes gene expression. (b) ERE independent genomic pattern. E2 activated ER binds with other classes of transcription factors, thereby regulating gene expression. (c) Ligand independent genomic pattern. Peptides such as EGF, and IGF-1 can activate estrogen receptors to express target genes. Phosphorylation of estrogen receptors may be the key factor. (d) mER-mediated signaling pathway. E2-mER mediated signal transduction causes a rapid regulation effect of the cellular response. E2:17β-estradiol; ER: estrogen receptor; GPR30: G protein coupled estrogen receptor; ERE: estrogen response element; TF: transcription factor; P: phosphate group.