Hair follicles are known to constantly cycle through phases of accelerated growth (called ‘anagen’), regression (‘catagen’), and rest (‘telogen’). This cycle and the balance between successive steps are thought to be maintained by a delicate balance between hormones, nutrition, and environmental exposures. In today’s increasingly polluted world, plagued with suboptimal dietary choices, hair conditions, including alopecia, are steadily increasing in prevalence, substantially impacting patients’ quality of life. Dermal papilla (DEP) cells are the best-studied cell types involved in hair follicle function and eventual hair growth. These cells have previously been implicated in hair growth factor production and hair follicle cycle modulation, highlighting the potential of leveraging these cells for beneficial hair growth outcomes.
Gut microbial research is increasingly substantiating the close association between gut health and hair growth. Biotin (vitamin B7) and Equol are two well-known gut microbiota-derived bioactives that have been shown to have benefits for hair condition. Unfortunately, the mechanisms by which these benefits arise remain poorly understood. Recent research has increasingly investigated the role of 5-hydroxytryptamine (5-HT) in skin and hair biology. Commonly called ‘serotonin’, this neurotransmitter is best known for its mood and gastrointestinal activities, but its hair growth potential remains unknown. Identifying potential uses for serotonin in hair treatment would reduce our dependence on synthetic drugs like minoxidil or pave the way to combination therapies with substantially improved efficacy.
In a recent study published in the journal Scientific Reports, researchers investigated how serotonin may also impact hair growth. Using gene expression analysis and hair follicle cultures, the study revealed that serotonin signaling activates dermal papilla (DEP) cells and upregulates key genes associated with hair growth, thereby promoting hair shaft elongation. Their findings suggest that serotonin and related compounds may lead to new treatments for hair loss disorders, such as alopecia. The present study leverages several experimental models (2D monolayer cultures, 3D follicle organoids [follicloids], and actual human hair follicles from patients with androgenic alopecia [AGA]) to investigate whether activating serotonin signaling in DP cells or treating them with a 5-HT receptor (HTR) agonist could promote hair growth.
The HTR agonist used in these assays is sumatriptan, an anti-migraine drug that targets HTR1B/1D receptors and has not been previously used in hair follicular investigations. Serotonin treatment prompted robust activation of hair growth-related genes in DEP cells. Alkaline phosphatase (ALP) and vascular endothelial growth factor A (VEGFA) expression, both indicators of follicular activity, were observed to increase significantly, with statistical significance for VEGFA starting at 50 μM and for ALP at 100 μM. RNA-seq results confirmed these findings and further demonstrated the upregulation of the calcium/cAMP signaling pathways. Scientists propose that these pathways serve as secondary messengers in serotonin signaling and are recognized hallmarks of follicular activity.
ImageJ-monitored results were no less impressive – hair follicle organoids (hair follicloids) treated with 100 μM 5-HT showed significantly elongated sprouting structures compared to no serotonin. Interestingly, while growth rates were comparable across treatments for the first three days, average sprout lengths increased steadily from day 4 to day 10, indicating both time- and dose-dependent growth responses. Encouragingly, these results were replicated in human follicle organ cultures, suggesting serotonin’s potential clinical applications for mitigating hair loss. However, the authors emphasize that these findings are accompanied by important caveats. The effective serotonin concentrations used in the study are orders of magnitude higher than those normally found in the skin.
Such high doses could lead to ‘Serotonin syndrome,’ a condition with serious psychiatric and neuromuscular symptoms. Complicating the picture further, the researchers note that some existing drugs that increase serotonin, known as SSRIs, have been reported to cause hair loss in certain individuals. Unexpectedly, sumatriptan succinate replicated serotonin’s effects almost identically. While the mechanisms of these interactions remain unknown, these findings suggest that sumatriptan succinate may form a viable repositioned drug for patients with known reactions to common minoxidil- or oxytocin-based interventions. If future research can determine the mechanism of serotonin’s efficacy, and establish a safe method of application that avoids the risks associated with high concentrations.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Scientific references
Kageyama T, Seo J et al. Sci Rep. 2025; 15:24525.
Kageyama T, Miyata H et al. Sci Rep. 2023; 13:4847.
Grymowicz M et al. Int J Molec Sci. 2020; 21:5342.
