# Tropic Roles for Leptin in the Maturation of Somatotropes

> **NIH NIH R01** · UNIV OF ARKANSAS FOR MED SCIS · 2020 · $444,315

## Abstract

PROJECT SUMMARY/ABSTRACT
Metabolic health is critically dependent on tropic actions by the adipokine leptin, which programs the
hypothalamus during perinatal development to receive normal metabolic signals. Anterior pituitary
somatotropes are dependent on leptin for normal metabolic functions, however, the developmental timing of
this leptin dependency and underlying mechanisms represent a gap in our knowledge of leptin's broader roles.
The overall objective of this application is to ascertain the importance of the neonatal surge of leptin to
somatotrope maturation. Our first hypothesis states that normal somatotrope maturation is dependent
on perinatal leptin signals and that lack of early leptin signals alters adult somatotrope
functions. Our second hypothesis states that leptin regulates somatotropes through effector
pathways involving the POU1F1/PIT1 transcription factor, the mRNA translational control
protein, Musashi (MSI) and regulatory microRNAs (miRNAs). Two aims will test these hypotheses:
Aim 1 studies will determine how the loss of leptin signals impacts neonatal maturation of
somatotropes and their metabolic functions in the adult. We will study the neonatal development of
somatotropes in animal models in which leptin signals are either: 1) deleted following the somatotrope-
selective ablation of Lepr exon 1; 2) blocked by a leptin antagonist during the leptin surge or 3) attenuated by
maternal undernutrition. We will replace neonatal leptin in the undernourished animals to test the hypothesis
that early leptin signaling is vital for neonatal maturation of somatotropes and their normal function in the
adult. Aim 2 studies will identify mechanisms underlying the leptin regulation of somatotropes.
These studies will use purified populations of somatotropes to determine if leptin's actions are mediated by
signaling pathways that attenuate MSI-mediated repression of Pou1f1, Tsh, and Prl mRNAs. We will also study
miRNA-mediated repression of Gh and Ghrhr mRNAs and will employ unbiased approaches to identify
additional novel leptin-dependent mechanisms controlling somatotrope maturation. This contribution is
significant because it addresses the global problem of the importance of leptin in the prevention of the
metabolic dysfunction caused by maternal undernutrition, which contributes to 11% of the total global disease
burden, ultimately leading to 35% of child deaths. The proposed research is conceptually innovative because it
broadens our understanding of leptin actions to include cells in the anterior pituitary that are known to be
important metabolic sensors, and introduces novel regulatory pathways for leptin and utilizes methodological
advancements in the purification of somatotropes. The expected outcomes of the work are that (1) the findings
will fully inform the field about leptin's tropic role in somatotrope maturation and function and (2) this work
will provide information about mechanisms of leptin's action that may be targeted...

## Key facts

- **NIH application ID:** 9912144
- **Project number:** 5R01DK113776-04
- **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:** $444,315
- **Award type:** 5
- **Project period:** 2017-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9912144

## Citation

> US National Institutes of Health, RePORTER application 9912144, Tropic Roles for Leptin in the Maturation of Somatotropes (5R01DK113776-04). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/9912144. Licensed CC0.

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