Sam Thilmany (Cologne / DE; Bonn / DE), Andreas Thomas (Cologne / DE), Yvonne Reinders (Dortmund / DE), Matthias Vogel (Bonn / DE), Catharina Scholl (Bonn / DE), Albert Sickmann (Dortmund / DE), Mario Thevis (Cologne / DE)
Background
Since its introduction in 1960, hormonal contraception has been a groundbreaking advancement in women's sexual autonomy and a cornerstone in preventing unintended pregnancies. Even today, after over six decades, oral hormonal contraception remains a pivotal method in many Western nations.
However, hormonal contraception has also presented challenges. Early concerns about severe adverse reactions, such as thromboembolic events and an elevated risk of breast cancer, emerged. Additionally, emerging evidence suggests a potential link between hormonal contraception and adverse effects on mental health, including mood disturbances. Nevertheless, epidemiological studies have been divergent, suggesting that group-specific factors may complicate interpretation. Consequently, a definitive causal relationship has yet to be established.
This project seeks to deepen our understanding of the pharmacological effects of steroid receptor ligand administration on the neuronal proteome, aiming to elucidate potential functional changes within the central nervous system that may be associated with depressive disorders.
Methods
The ReNcell VM neuronal progenitor cell line was treated with estrogenic (ethynylestradiol), progestogenic (levonorgestrel), and androgenic (S-23) steroid receptor ligands. Treatment effects were analyzed by label-based and label-free quantitative bottom-up proteomics. Statistical analysis utilized Thermo Scientific Proteome Discoverer with Sequest HT and Chimerys and a tailored R script.
Results
Among all the quantified proteins, several hundred exhibited differential expression upon treatment with steroid receptor ligands. Gene Ontology analysis revealed significant regulation in biological processes, including regulation of neurotransmitter uptake, cell-substrate adhesion, and gliogenesis. Essential molecular functions were integrin binding and S100 protein binding. Regulated cellular components included the collagen-containing extracellular matrix and focal adhesion. These findings provide insights into molecular mechanisms underlying depression-related changes, highlighting pathways involved in cell adhesion and neurotransmitter regulation.