# Transcriptional networks coordinating luminal environment in the human epididymis: the role of the androgen receptor.

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2020 · $345,792

## Abstract

SUMMARY: Androgens are steroid hormones with a pivotal role in determining male characteristics, which
bind to the androgen receptor (AR) to direct a unique transcriptional program. Although best studied in the
human prostate and in prostate cancer, the AR transcriptional network also controls normal functions of other
male reproductive tract tissues, including the epididymis and the vas deferens. A critical function of the
epididymis, the proximal part of the male genital ducts that transport testicular products out of the body, is in
sperm maturation. Immature sperm leaving the testis acquire the capacity to fertilize an egg during their
passage through the head and body of the epididymis. Many factors contribute to establishing and maintaining
the specific epididymis luminal environment that is required for normal sperm maturation. These include
hormones and other testicular products that enter the duct, though the epithelium lining the epididymis has a
pivotal role. The proximal luminal fluid has a low pH and bicarbonate concentration to preserve sperm motility
and relatively high potassium concentrations to facilitate sperm quiescence. Multiple ion channels, ion
exchangers, transporters and water channels in the apical or basolateral membranes of the epididymis
epithelium participate in fine-tuning the luminal fluid. Building upon a) substantial preliminary data on the AR
transcriptional network in human epididymis epithelial (HEE) cells, which suggest novel co-factors for this TF
are involved in the epididymis, together with b) an innovative HEE organoid model, our goal is to test the
overarching hypothesis that the Androgen Receptor is pivotal to establishing and maintaining normal functions
of the human epididymis epithelium. Moreover, that through the recruitment of specific co-factors, AR
orchestrates a unique transcriptional program in this tissue. In the first specific aim we will determine the
mechanisms through which androgens impact the differentiation and function of the human epididymis
epithelium. We will use a novel epididymis organoid model for functional studies together with single cell RNA-
sequencing (scRNA-seq). These experiments will provide novel and important insights into the role of
androgens in the biology of the human epididymis epithelium and the transcriptional network that coordinates
its functions. Studies in the second aim will determine the mechanisms of interaction of AR with other co-
factors including RUNX1 and CEBPβ and how these factors integrate into the transcriptional network in the
human epididymis epithelium. We will also investigate the hierarchy of dependency of AR, RUNX1 and
CEBPβ using genome wide and locus-specific assays. A gene of particular interest is the cystic fibrosis
transmembrane conductance regulator (CFTR), which establishes and maintains chloride and bicarbonate
gradients in the epididymis lumen. CFTR recruits a unique set of cis-regulatory elements in HEE cells, some of
which also ...

## Key facts

- **NIH application ID:** 9971855
- **Project number:** 2R01HD068901-06A1
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Ann Harris
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $345,792
- **Award type:** 2
- **Project period:** 2011-08-10 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971855

## Citation

> US National Institutes of Health, RePORTER application 9971855, Transcriptional networks coordinating luminal environment in the human epididymis: the role of the androgen receptor. (2R01HD068901-06A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9971855. Licensed CC0.

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