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Gonadal hormone deprivation regulates response to tibolone in neurodegenerative pathways

Andrew J McGovern1, Maria Angeles Arevalo2, Sergio Ciordia3

  • 1Department of Biological Sciences, Faculty of Science and Engineering, University of Limerick, Limerick, Ireland.

The Journal of Steroid Biochemistry and Molecular Biology
|April 13, 2024
PubMed

Insights

Gonadal hormone deprivation impacts brain molecular environment, altering hormone therapy (HT) effectiveness. This study reveals Tibolone

Area of Science:

  • Neuroendocrinology
  • Molecular Neuroscience
  • Proteomics

Background:

  • Gonadal hormone deprivation (GHD) increases neurodegeneration risk.
  • Hormone therapies (HTs) have variable efficacy, influenced by sex, drug, and timing.
  • Brain molecular environment changes post-GHD, affecting HT response.

Purpose of the Study:

  • Investigate the impact of GHD on the brain's molecular response to Tibolone.
  • Identify molecular mechanisms underlying variable HT efficacy.
  • Explore precision medicine approaches for HTs in neurodegeneration.

Main Methods:

  • Utilized a mouse model of GHD treated with Tibolone.
  • Performed proteomic analysis to identify protein changes.
  • Employed network pharmacology to analyze pathway interactions.

Main Results:

  • Identified a reprogrammed Tibolone response in the GHD brain.
  • Discovered altered responses in neurodegeneration, cellular respiration, and homeostasis pathways.
  • Found 23 proteins with GHD/sex-dependent Tibolone responses, affecting oxidative phosphorylation and calcium signaling.

Conclusions:

  • Therapeutic efficacy of HTs is contingent on GHD and sex.
  • Precision medicine is crucial for optimizing HTs.
  • Further research is needed to elucidate underlying mechanisms of variable HT response.
Keywords:
GonadectomyHormone TherapyMenopauseNeurodegenerationProteomicsTibolone

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