Dataset Information

Hormonal contraceptives and depression: A proteomic analysis using neuronal models

ABSTRACT: Purpose: Hormonal contraceptives are linked to a higher prevalence of depressive symptoms. Given their popularity in Western countries, understanding the biochemical effects on neuronal cells is crucial to minimizing mental health risks.Experimental design: Neural progenitor cells were treated with ethinyl estradiol (EE) and levonorgestrel (LNG), two synthetic sex hormones commonly used in oral contraception, and S-23, a selective androgen receptor modulator developed as a potential synthetic sex hormone for male hormonal contraception. Label-based quantitative proteomics with the TMTpro 16plex tandem mass tags was used to assess protein expression changes between treated and untreated cells.Results: Treatment of human neural progenitor cells with EE, LNG, EE + LNG, and S 23 led to distinct and overlapping proteomic changes, with enrichment in pathways related to inflammation, oxidative stress, transcriptional regulation, and cell death. Disease association analyses linked these changes to neurodegenerative and psychiatric conditions, including mechanisms relevant to depression.Conclusions and Clinical Relevance: These findings suggest that hormonal compounds used in contraception and performance enhancement may influence molecular pathways implicated in mental health, particularly depression. While not directly translatable to clinical outcomes, the results support the need for further investigation into the neuropsychiatric effects of hormonal treatments.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Neural Progenitor Cell

SUBMITTER: Sam Thilmany

LAB HEAD: Mario Thevis

PROVIDER: PXD056721 | Pride | 2026-01-05

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

Items per page:

1 - 5 of 43

Publications

Hormonal Contraceptives and Depression: A Proteomic Analysis Using Neuronal Models.

Thilmany Sam S Thomas Andreas A Reinders Yvonne Y Shakeri Farhad F Vogel Matthias M Sickmann Albert A Scholl Catharina C Thevis Mario M

Proteomics. Clinical applications 20250910 1

<h4>Purpose</h4>Hormonal contraceptives are linked to a higher prevalence of depressive symptoms. Given their popularity in Western countries, understanding the biochemical effects on neuronal cells is crucial to minimizing mental health risks.<h4>Experimental design</h4>Neural progenitor cells were treated with ethinyl estradiol (EE) and levonorgestrel (LNG), two synthetic sex hormones commonly used in oral contraception, and S-23, a selective androgen receptor modulator developed as a potentia ...[more]

PMID: 40931400

Similar Datasets

Project description:Huntington’s disease is a fatal autosomal dominant neurodegenerative disorder, characterized by neuronal cell loss, primarily in the striatum, cortex, and hippocampus, causing motor, cognitive, and psychiatric impairments. Unfortunately, no treatments are yet available to modify the progression of the disease. Recent evidence from Huntington’s disease mouse models suggests that protein phosphorylation (catalysed by kinases and hydrolysed by phosphatases) might be dysregulated, making this major posttranslational modification a potential area of interest to find novel therapeutic targets. Furthermore, environmental enrichment (EE), used to model an active lifestyle in preclinical models, has been shown to alleviate Huntington’s disease-related motor and cognitive symptoms. However, the molecular mechanisms leading to these therapeutic effects are still largely unknown. In this study, we applied a phosphoproteomics approach combined with proteomic analyses on brain samples from pre-motor symptomatic R6/1 Huntington’s disease male mice (HD mice) and their wild-type (WT) littermates, after being housed either in EE conditions, or in standard housing (SH) conditions from 4 to 8 weeks of age (n=6 per group). We hypothesised that protein phosphorylation dysregulations occur prior to motor onset in this mouse model, in two highly affected brain regions, the striatum and hippocampus. Furthermore, we hypothesised that these phosphoproteome alterations are rescued by EE. When comparing 8-week-old HD mice and WT mice in SH conditions, our analysis revealed 229 differentially phosphorylated peptides in the striatum, compared to only 15 differentially phosphorylated peptides in the hippocampus (statistical thresholds FDR0.05, FC1.5). At the same disease stage, minor differences were found in protein expression, with 24 and 22 proteins dysregulated in the striatum and hippocampus, respectively. Notably, we found no differences in striatal protein phosphorylation and protein expression when comparing HD mice and their WT littermates in EE conditions. In the hippocampus, only four peptides were differentially phosphorylated between the two genotypes under EE conditions, and 22 proteins were differentially expressed. Together, our data indicates that protein phosphorylation dysregulations occur in the striatum of HD mice, prior to motor symptoms, and that the kinases and phosphatases leading to these changes in protein phosphorylation might be viable drug targets to consider for this disorder. Furthermore, we show that an early environmental intervention was able to rescue the changes observed in protein expression and phosphorylation in the striatum of HD mice and might underlie the beneficial effects of EE, thus identifying novel therapeutic targets.

			Action	DRS
	LBQ.msf	Msf
	LBQ_sample_1_1.raw	Raw
	LBQ_sample_1_2.raw	Raw
	LBQ_sample_1_3.raw	Raw
	LBQ_sample_1_4.raw	Raw