# Glucocorticoid receptor phosphorylation in endocrine adaptation to stress

> **NIH NIH R56** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $495,420

## Abstract

Project Summary
Glucocorticoids exert many effects in the central nervous system ranging from spatial learning and cognition to
stress and depression. Interestingly, the effects of glucocorticoids upon neuronal circuits are also strongly
influenced by neurotrophins, such as Brain Derived Neurotrophic Factor (BDNF). We have identified a novel
pathway of communication between glucocorticoids and BDNF such that BDNF-signaling increased GR
phosphorylation at serines 155 (S155) and 287 (S287). This altered the repertoire of genes controlled by GR,
and disruption of the GR phosphorylation sites impaired neuroplasticity upon chronic stress. The goal of this
proposal is to understand the physiological relevance of GR phosphorylation at S155 and S287 in
neuroendocrine adaptation to stress in vivo using a newly developed GR phosphorylation-site-deficient
(S155A/S287A) knock-in mouse, as well as the molecular mechanisms involved in phosphorylation-dependent
regulation of GR-mediated gene expression. Our approaches include molecular, imaging and behavioral
studies, genome wide assessment of GR target genes and receptor occupancy, as well as analysis of synaptic
plasticity upon stress using two photon microscopy in the unique GR S155A/S287A knock-in mouse model.
We will also examine whether GR pS155/pS287 is altered in PBMCs of depressed versus not depressed
humans to lend relevance of this pathway to human behavior. Our studies will illuminate the genomic networks
by which GR pS155/pS287 controls neuroendocrine adaptation to stress.

## Key facts

- **NIH application ID:** 9883840
- **Project number:** 5R56MH115281-02
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Michael J. Garabedian
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $495,420
- **Award type:** 5
- **Project period:** 2019-03-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9883840

## Citation

> US National Institutes of Health, RePORTER application 9883840, Glucocorticoid receptor phosphorylation in endocrine adaptation to stress (5R56MH115281-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9883840. Licensed CC0.

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