# Control of pituitary cell plasticity through regulated mRNA translation

> **NIH NIH R01** · UNIV OF ARKANSAS FOR MED SCIS · 2020 · $640,717

## Abstract

SUMMARY
The anterior pituitary functions as the endocrine core of the organism, regulating hormonal synthesis and
secretion to effect adaption to changing metabolic and reproductive needs. Deficiencies of pituitary-derived
hormones, due to genetic causes, head injury, under or over-nutrition, or as a consequence of pituitary cancer
treatment cause severe morbidity. The cells of the anterior pituitary have been long known to possess
remarkable plasticity of fate suggesting the presence of stem cell-like cell populations. However, whether stem
cells do indeed contribute to cell plasticity and pituitary recovery and the underlying mechanisms that control
pituitary cell plasticity in response to pituitary injury, changing hormonal demands or tumor progression have
not been established. The mRNA translation control protein, Musashi, has been shown to plays a critical role
in mediating physiological and pathological stem cell function in many tissue types. Musashi mediates stem
cell self renewal by repressing translation of target mRNAs that encode proteins required for cell cycle
inhibition and cell differentiation. Our data indicate that Musashi is broadly expressed in the adult anterior
pituitary in non-stem cell populations, as well as in pituitary stem cells.
The overall objective of this application is to assess the role of regulated mRNA translation in general, and the
Musashi protein specifically, in mediating adaptive changes of cell fate in the pituitary. The central hypothesis
is that Musashi controls both pituitary stem/progenitor cell differentiation and also plasticity
of hormone producing cells in the adult pituitary. Specifically, studies for Aim 1 will use both in vivo
mouse models and cell culture approaches to test the hypothesis that Musashi regulates cell plasticity during
tissue regeneration as well as developmental pituitary stem/progenitor cell function. Studies for Aim 2 will use
unbiased polysome-based, RNA-sequencing approaches to test the hypothesis that Musashi has gender-specific
mRNA targets and RNA-targeting mechanisms that control cell fate decisions in stem/progenitor cells and in
adaptive responses of adult hormone-producing cell populations.
The findings from this study will fully inform the field about the role of Musashi activity and mRNA translation
in the control of pituitary cell plasticity and stem/progenitor cell function. Furthermore, these proposed studies
relate to therapeutic approaches for endocrine and metabolic diseases, specifically caused by pituitary
deficiencies. As hormone replacement strategies do not fully mimic physiological pulsatile secretion regimes,
studies that promote regeneration of missing endocrine cell lineages would be a significant clinical
improvement. This will positively impact gender-appropriate treatment paradigms for combined pituitary
hormone deficiency, metabolic disease and pituitary tissue repair after head injury.

## Key facts

- **NIH application ID:** 9969085
- **Project number:** 5R01HD093461-03
- **Recipient organization:** UNIV OF ARKANSAS FOR MED SCIS
- **Principal Investigator:** GWEN V CHILDS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $640,717
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9969085

## Citation

> US National Institutes of Health, RePORTER application 9969085, Control of pituitary cell plasticity through regulated mRNA translation (5R01HD093461-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9969085. Licensed CC0.

---

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