# Cell specific expression in the pituitary gland

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $377,487

## Abstract

Abstract
Pituitary gland dysfunction affects growth, fertility, the stress response, and many other physiological functions.
Hypopituitarism can result from congenital defects in organ development (about 1/4000 births) and from
pituitary adenomas, which are among the most common type of intracranial tumor. Treatment involves
hormone replacement therapy, which can involve daily injections of recombinant growth hormone at great
expense per patient. Some adenomas respond to pharmacological therapy, while others are recurrent,
potentially causing disfigurement, multiple trans-sphenoidal surgeries, and can result in blindness and death.
Genetically engineered mice have been used to identify the roles of several transcription factors and signaling
molecules in differentiation, and there is excellent correspondence to human pituitary disorders. In previous
years of this grant we used mouse mutants to define the roles of several transcription factors (PITX2, GATA2,
FOXL2, LHX3, LHX4 and ISL1) and signaling pathways (BMP, FGF, WNT) in pituitary development and
disease. We also determined how the transcription factor mutations affected expression of cell cycle
regulators to cause pituitary hypoplasia, and identified a novel gene that drives cell proliferation in a mouse
model of thyrotrope adenoma. The long-term goal of this research is to improve diagnosis and therapy for
people with genetic or acquired pituitary disease by increasing our fundamental understanding of how pituitary
growth and cell specification are orchestrated at the molecular level. The overall objectives of this application
are: to define the roles of two key transcription factors, Isl1 and Zeb2, in pituitary development and disease,
and to employ an unbiased approach to identify novel transcription factors, lncRNA and chromatin changes
that drive pituitary thyrotrope cell fate and establishment of robust hormone production. We generated the first
model of Rathke's cleft cysts by deleting Isl1 in pituitary development, and we have evidence that this leads to
misregulation of pituitary stem cells and formation of adenomas. We also show that Zeb2 is necessary to drive
an epithelial to mesenchymal-like transition (EMT) in pituitary stem cell cultures. The proposed research uses
up to date approaches for analysis of Isl1 and Zeb2. It is innovative because it uses an unbiased approach to
discovering new factors and pathways, including exploring the role of noncoding RNAs, which is a relatively
new area of investigation, and it uses state of the art genomic analysis techniques to identify regulatory regions
of genes, which are likely sites of mutations in patients with hypopituitarism or adenoma risk factors. This
research will be significant because it will provide fundamental information about the molecular mechanisms of
formation of pituitary cysts and adenomas, the regulation of EMT, and it will establish the regulatory
mechanisms underlying thyrotrope fate. This information will contribu...

## Key facts

- **NIH application ID:** 10143263
- **Project number:** 5R01HD034283-25
- **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:** $377,487
- **Award type:** 5
- **Project period:** 1999-07-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10143263

## Citation

> US National Institutes of Health, RePORTER application 10143263, Cell specific expression in the pituitary gland (5R01HD034283-25). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10143263. Licensed CC0.

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