# Hypopituitarism: role of PROP1 and retinoic acid signaling in regulation of pituitary stem cell differentiation

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $432,124

## Abstract

Hypopituitarism: role of PROP1 and retinoic acid signaling in regulation of pituitary stem cell
differentiation
Abstract
Our overarching goal is to understand the molecular basis of pituitary insufficiency (hypopituitarism) in humans
and mice. The rationale behind this goal is that a molecular understanding of this common birth defect
affecting 1/4000 children will yield 1) fundamental information about organogenesis, 2) diagnoses with value
for predicting risk and monitoring progression, and 3) ultimately provide insight about therapeutic approaches
that could aid children with congenital problems as well as adults with acquired pituitary dysfunction. Mutations
in thirty genes are reported to cause hypopituitarism and growth insufficiency, yet the majority of the patients
remain with no molecular diagnosis. Mutations in the pituitary-specific transcription factor PROP1 are the most
common known cause of hypopituitarism in humans. Prop1 is the first pituitary-specific gene in the hierarchy
of transcription factors that regulate pituitary development. We established a role for Prop1 in regulating the
transition of pituitary stem cells to hormone-producing cells in an epithelial to mesenchymal-like transition
process, which is a component of both organogenesis and the transition to invasive cancer in other organ
systems. At least two direct targets of Prop1 cause hypopituitarism when mutated, the genes encoding the
transcription factors POU1F1 and HESX1. We propose to test the following hypotheses: 1) PROP1 has a
dual role in pituitary development. Embryonic expression of Prop1 is necessary for driving pituitary placode
fate and suppressing differentiation into inappropriate cell fates, while postnatal expression of Prop1 is
important for replenishment of hormone-producing cells from stem cell pools, and 2) PROP1 is required to
stimulate retinoic acid signaling, which drives stem cells to transition to differentiate into the POU1F1 lineage,
and 3) stem cell expression profiling will reveal novel candidate genes and pathways that regulate organ
development and maintenance, and provide candidate genes for cases of hypopituitarism with no known
diagnosis. We will conduct functional studies in mouse models and apply state of the art single cell
sequencing technology, revealing the roles of PROP1 and retinoic acid signaling in pituitary development and
function. Completion of these goals will provide fundamental information on pituitary precursor cell generation
and proliferation and contribute to better understanding of the genetic and environmental factors that contribute
to pituitary hormone deficiency.

## Key facts

- **NIH application ID:** 10113655
- **Project number:** 5R01HD097096-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Sally A. Camper
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $432,124
- **Award type:** 5
- **Project period:** 2019-03-04 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10113655

## Citation

> US National Institutes of Health, RePORTER application 10113655, Hypopituitarism: role of PROP1 and retinoic acid signaling in regulation of pituitary stem cell differentiation (5R01HD097096-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10113655. Licensed CC0.

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