PhD defence
The role of glucocorticoid receptor signaling in metabolic disease: A matter of time and sex
- S. Li
- Date
- Wednesday 23 April 2025
- Time
- Location
-
Academy Building
Rapenburg 73
2311 GJ Leiden
Supervisor(s)
- Prof.dr. O.C. Meijer
- dr. J. Kroon
Summary
This thesis explores how sex and time influence glucocorticoid signaling, particularly its effects on metabolism in different tissues under pathological conditions. Our findings provide new insights into the variability of glucocorticoid responses, with potential implications for personalized medicine.
In Chapter 2, we identified sex differences in muscle atrophy and dysfunction following chronic glucocorticoid exposure in mice. Female mice exhibited reduced grip strength, while both sexes experienced muscle mass loss. Transcriptome analysis showed that male mice had more pronounced transcriptional changes, highlighting sex-specific responses to glucocorticoids in skeletal muscle.
Chapter 3 examined how the timing of synthetic glucocorticoid treatment affects metabolic side effects. We found that out-of-phase treatment with betamethasone induced insulin resistance and hyperinsulinemia, whereas in-phase treatment minimized these effects. These results emphasize the importance of aligning glucocorticoid therapy with endogenous circadian rhythms to reduce adverse metabolic outcomes.
In Chapter 4, we investigated glucocorticoid receptor (GR) signaling in a mouse model of polycystic ovary syndrome (PCOS). We observed upregulated GR-related genes in DHT-treated mice, suggesting a deregulated GR system. Treatment with a GR antagonist improved glucose metabolism, indicating that GR signaling contributes to PCOS-associated metabolic dysfunction.
Our research is socially relevant as it underscores the need for sex- and time-specific considerations in glucocorticoid therapy, potentially improving treatment strategies for metabolic diseases. By identifying factors that modulate glucocorticoid responses, our findings open avenues for more targeted and effective therapeutic approaches.
PhD dissertations
Approximately one week after the defence, PhD dissertations by Leiden PhD students are available digitally through the Leiden Repository, that offers free access to these PhD dissertations. Please note that in some cases a dissertation may be under embargo temporarily and access to its full-text version will only be granted later.
Press enquiries (journalists only)
General information
Beadle's Office
pedel@bb.leidenuniv.nl
+31 71 527 7211