# Growth hormone actions in prostate carcinogenesis

> **NIH NIH R21** · UNIVERSITY OF WISCONSIN-MADISON · 2021 · $206,962

## Abstract

Abstract
The growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis has been implicated in age related diseases
including prostate cancer. Humans with Laron syndrome lack functional growth hormone receptors (GHRs) and
have reduced rates of cancer and diabetes. Mice with homozygous null mutations in Ghr are also protected from
cancer in the C3(1)/TAg prostate cancer model. Similarly, rats lacking a functional GH gene are protected
prostate cancers in the Probasin/TAg model. GHRs are expressed in multiple tissues including the liver and
prostate. Activation of GHRs in the liver by GH is the main mechanism that stimulates the release of IGF-1 into
circulation. Many GH actions are mediated by the subsequent actions of IGF-1 in target tissues including the
prostate. Furthermore, evidence from humans indicates that elevated circulating IGF-1 confers an increased risk
for the development of several cancers including prostate cancer. The expression of GHRs in the normal prostate
and by prostate cancer cells suggests that local signaling by GHRs may also be important in prostate cancer
cells. Recent studies demonstrating that up-regulation of local GH synthesis by prostate cancer cells is a
common feature of cancer progression further supports the potential importance of local GH/GHR actions in
prostate cancer. However, several important aspects of the role of GH/IGF-1 axis in prostate cancer remain
uncertain. Available studies have not addressed the potential ongoing requirement for GH signaling at different
stages of prostate cancer progression, the role of local GHR signaling in prostate cancer cells, or the signal
transduction mechanisms downstream of GHR activation important in prostate cancer. This project will use
innovative genetic approaches in mice to address these limitations of current knowledge. Previous rodent studies
were also limited because they focused only on tumors driven by disruption the function of the TP53 and RB1
tumor suppressors. This project will further determine if the requirement for intact GHR signaling extends to
mouse models for prostate cancers driven by activation of the PI3K/AKT pathway that is also commonly observed
in human prostate cancers. Completion of these studies will be an important step toward identifying the best
ways to employ pegvisomant or other agents targeting the GH/IGF-1 axis for the treatment and/or prevention of
prostate cancer.

## Key facts

- **NIH application ID:** 10063500
- **Project number:** 5R21CA238105-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Paul C Marker
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $206,962
- **Award type:** 5
- **Project period:** 2019-12-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10063500

## Citation

> US National Institutes of Health, RePORTER application 10063500, Growth hormone actions in prostate carcinogenesis (5R21CA238105-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10063500. Licensed CC0.

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