# Role of Estrogen Signaling in Notch Pathway Activation in Sertoli Cells

## TL;DR

This study shows that estrogen signaling through specific receptors influences the Notch pathway in Sertoli cells, which is important for testicular function and sperm production.

## Contribution

The study reveals a novel mechanism of estrogen action via nuclear receptors in regulating the Notch1 pathway in Sertoli cells.

## Key findings

- 17β-estradiol enhances Notch1 activation and Hes1 expression via estrogen receptor 2.
- Estrogen receptor 1 reduces Hey1 expression in Sertoli cells.
- G protein-coupled estrogen receptor 1 does not significantly affect Notch1 signaling in these cells.

## Abstract

Sertoli cells constitute a somatic component of seminiferous epithelium in mammalian testis which supports the process of spermatogenesis. These cells are sensitive not only to the male sex hormones androgens, but also to their metabolites, estrogens. In this study, we aimed to explore the action of estrogen signaling in rodent Sertoli cells on the activity of canonical Notch pathway, which provides contact-dependent communication between the cells of seminiferous epithelium. Experiments performed on Sertoli cell line and primary Sertoli cell cultures demonstrated that 17β-estradiol, acting through estrogen receptor 2, enhances Notch1 activation, transcriptional activity of recombination signal binding protein for immunoglobulin kappa J region (RBPJ), interaction of RBPJ with Hes1 promoter, and the expression of the Hes1 effector gene and protein. On the other hand, 17β-estradiol by binding to estrogen receptor 1 reduces the expression of the Hey1 effector gene. In contrast to nuclear estrogen receptors, no evident role of G protein-coupled estrogen receptor 1 in regulating Notch1 signaling activity in Sertoli cells has been found. The data presented indicate the role of nuclear estrogen receptor signaling in the control of Notch1 pathway activity in Sertoli cells, and thus reveal new mechanism of estrogen action in maintaining homeostasis of the seminiferous epithelium.

The online version contains supplementary material available at 10.1007/s43032-025-01901-y.