# Mediators for dynamic regulation of Star transcription in Leydig cells

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $562,494

## Abstract

7. Project summary/Abstract
Leydig cells within the testis are the source of androgens that promote virility at both fetal and adult
stages, but Leydig cell populations are distinct at each age. As such, adult and fetal Leydig cells function
to synthesize testosterone in distinct cellular and endocrine environments. The AIMs of this proposal are
focused on regulation of Star, the known gatekeeper in controlling access of cholesterol to enzymatic
activity of the series of steroidogenic enzymes required for conversion to testosterone. Here we focus on
novel regulatory events that exert dynamic interactions with Star chromosomal loci that will explain how
fluctuating Star transcript accumulation can relate to changes in androgen synthesis. Previously, we
used high-resolution fluorescent in situ hybridization (HR-FISH) to localize and quantify a unique pattern
for primary, spliced, and mRNA species accumulation for Star compared to other steroidogenic genes
within single Leydig cells. We will use this and other innovative techniques to compare results from
studies that investigate individual adult and fetal Leydig cells in vitro, within MA10 cells and primary
cultures, and in vivo, within whole testes. Pulsatile LH stimulates primarily cAMP/PKA signals to promote
testosterone synthesis in adult Leydig cells. While we have substantial means to explain how Star
transcription is turned ON by LH/PKA, we understand little about what happens when the pulse is
removed, and even less about the interpulse interval. In AIM 1, we will test the hypothesis that the events
occurring at Star loci during this interval are just as critical to controlling testosterone output as the initial
stimulus. Meanwhile, the external stimuli that maintain androgen synthesis in fetal Leydig cells are less
clear, but evidence points to paracrine signals, with PKA activity playing a role. Another paracrine factor,
Sertoli cell-derived Desert Hedgehog (Hh) is known to initiate fetal Leydig cell differentiation, but its role
in their maintenance has not been tested. Once differentiated, fetal Leydig cells produce androgens at a
steadily increasing rate until late gestation. Therefore, in AIM 2, we will test the hypothesis that regulatory
events on Star loci facilitate a controlled increase in androgens within the fetal Leydig cell that compare
to those that occur during the interpulse interval in adult Leydig cells. Our findings have the potential to
explain fundamental biology underlying steroidogenic control and will have a profound impact on our
ability to explore mechanisms by which disturbances in testosterone synthesis, as in endocrine
disruption, cause significant clinical ramifications in males from all stages of life.

## Key facts

- **NIH application ID:** 9924272
- **Project number:** 5R01HD090660-04
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** COLIN ROBERT JEFCOATE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $562,494
- **Award type:** 5
- **Project period:** 2017-08-16 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9924272

## Citation

> US National Institutes of Health, RePORTER application 9924272, Mediators for dynamic regulation of Star transcription in Leydig cells (5R01HD090660-04). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/9924272. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*