# The Role of TSH-beta Splice Variant in Health and Disease

> **NIH NIH R21** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2020 · $193,125

## Abstract

PROJECT SUMMARY/ABSTRACT
Although it has been known for over three decades that thyrotropin (thyroid stimulating hormone [TSH])
is produced by cells of the immune system, the physiologic significance of that remains unclear. Studies
in our laboratory demonstrated that cells of the immune system produce a novel TSH splice variant
(TSHv), the first functional splice variant of TSH to be identified for mice and humans. Importantly, this
is the sole form of TSH produced by the immune system. We demonstrated that TSHβv expression is
increased in the thyroid of mice infected with reovirus or L. monocytogenes, due principally to the
trafficking of TSHβv-producing cells to the thyroid during infection. Based on those and other studies, we
propose that immune system TSHv plays a key role in regulating host metabolic activity by modulating
thyroid hormone synthesis. In this R21 grant, we will test the hypothesis that suppression of TSHβv
expression in the cells of the immune system will cause dysregulated thyroid hormone synthesis, altered
host metabolic activity, and disrupted bone morphogenesis in mice under normal healthy conditions, and
in pathophysiologic settings during infection. There are two Specific Aims for the project. Aim 1 To
assess the effects of TSHv suppression on basal metabolism, thyroid hormone synthesis, and bone
morphogenesis in normal mice. Aim 2. To assess the effects of TSHv knockdown on basal metabolism,
thyroid hormone synthesis, and bone morphogenesis during viral and bacterial infection. We will use two
approaches to suppress TSHβv. In the first, shRNA-TSHv lentivirus will be used to suppress TSHβv in
bone marrow hematopoietic cells and peripheral leukocytes. In the second, we will knockout TSHβv in
animals by Crispr/Cas9 gene editing. These studies will be the first to directly examine the functional
involvement of immune system TSHβv during normal homeostatic conditions and during times of
immunological stress. They are expected to greatly expand our knowledge of immune-endocrine
interactions in ways not appreciated to the present.

## Key facts

- **NIH application ID:** 9831128
- **Project number:** 5R21AI133313-02
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** JOHN R KLEIN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $193,125
- **Award type:** 5
- **Project period:** 2018-12-03 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9831128

## Citation

> US National Institutes of Health, RePORTER application 9831128, The Role of TSH-beta Splice Variant in Health and Disease (5R21AI133313-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9831128. Licensed CC0.

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