# Molecular mechanisms of pituitary plasticity

> **NIH NIH R01** · UNIV OF ARKANSAS FOR MED SCIS · 2024 · $632,540

## Abstract

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. The distinct pituitary hormone-
producing cell populations are known to possess remarkable plasticity of fate. However, the underlying
mechanisms that mediate pituitary cell plasticity in response to changing hormonal demands have not been
established, which is a major gap in knowledge. While it is recognized that stem cell differentiation and
cellular homeostasis are directed and regulated at multiple levels including gene transcription, signaling,
epigenetic and chromatin remodeling, these processes appear to be particularly sensitive to mechanisms that
impinge upon the control of mRNA translation. Identification of the molecular mediators that
regulate cellular plasticity within pituitary hormone-producing cell lineages would present a
valuable resource for therapeutic intervention to promote tissue regeneration or to oppose
cancer progression. The mRNA translation control protein, Musashi, plays a critical role in mediating
physiological and pathological stem cell function in many tissue types and has been shown to be broadly
expressed in the adult anterior pituitary in non-stem/progenitor cell populations to modulate hormone
expression. This study will focus on mechanisms by which Musashi differentially regulates distinct target
mRNAs, its mode of action and contribution to cell fate plasticity and its relevance to adult human pituitary
function. The long-term goal of this project is to determine the physiological mechanisms that control
pituitary cell fate determination. Specifically, 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. We will also perform an unbiased assessment on the role of transcriptional and post-
transcriptional control during hypothyroidism and lactation, known drivers of pituitary cell lineage plasticity.
The central hypothesis is that post transcriptional mechanisms are critical for the plasticity of
hormone producing cell lineages in the adult pituitary during adaptive responses to organismal
stress. We expect to fully inform the field about the molecular mechanisms underpinning Musashi target
mRNA-specific translational control. We will determine the relevance of Musashi-dependent control of human
pituitary mRNAs under physiological and pathological conditions and will elucidate in an unbiased manner the
molecular mechanisms controlling pituitary cell plasticity in response to changing hormonal demands.
Wherever possible, sex will be considered a variable. Findings from this study will positively impact
development of gender-specific therapeutic treatments for combined pituitary hormone deficiency and
pituitary tissue repair.

## Key facts

- **NIH application ID:** 11050356
- **Project number:** 1R01DK139476-01A1
- **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:** 2024
- **Award amount:** $632,540
- **Award type:** 1
- **Project period:** 2024-09-18 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11050356

## Citation

> US National Institutes of Health, RePORTER application 11050356, Molecular mechanisms of pituitary plasticity (1R01DK139476-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11050356. Licensed CC0.

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