The Hair Follicle and Hair Loss: A Review of DHT, Inflammation, Oxidative Stress, Vascular Signalling and the Biological Pathways Behind Hair Growth

Hair loss is a complex biological process involving interactions between androgen signalling, the hair-follicle cycle, dermal papilla cells, follicular stem cells, inflammatory pathways, oxidative stress, vascular signalling, prostaglandins, and multiple growth-regulating pathways. Although dihydrotestosterone (DHT) is a central factor in androgenetic alopecia, the published literature indicates that follicular miniaturisation cannot be explained by androgen signalling alone.

This narrative literature review examines the biological mechanisms involved in human hair-follicle growth, regression, cycling, and miniaturisation, with particular attention to the pathways implicated in androgenetic alopecia and related hair-growth biology.

The review examines the hair follicle as a dynamic regenerative structure and considers the roles of:

(A) the anagen, catagen, telogen, and exogen phases of the hair cycle;

(B) dermal papilla cells and epithelial-mesenchymal signalling;

(C) testosterone, 5-alpha-reductase, DHT, androgen receptors, and local androgen sensitivity;

(D) Wnt and beta-catenin signalling and its role in follicular regeneration;

(E) DKK-1 and CXXC5 as negative regulators of Wnt-related follicular signalling;

(F) hair-follicle stem cells and the signalling environment that regulates their activation;

(G) TGF-beta and BMP signalling and their roles in follicular regression, differentiation, and stem-cell regulation;

(H) IGF-1 and other growth-associated signalling pathways;

(I) VEGF, angiogenesis, vascular signalling, and changes in the perifollicular vascular environment;

(J) prostaglandins including PGD2, PGE2, PGF2alpha, and PGI2;

(K) inflammatory signalling, immune-cell activity, and perifollicular inflammation and fibrosis;

(L) oxidative stress, reactive oxygen species, antioxidant defence, mitochondrial dysfunction, and cellular senescence; and

(M) emerging molecular targets and the interaction between several of these pathways in androgenetic alopecia.

Particular attention is given to the relationship between androgen signalling and downstream follicular pathways. Published research has identified effects of DHT and androgen-receptor activation on dermal papilla cells, including changes involving TGF-beta, DKK-1, Wnt signalling, prostaglandins, vascular signalling, and other regulators of follicular growth. Research on CXXC5, Wnt and beta-catenin also provides evidence that suppression of regenerative signalling may contribute to follicular miniaturisation. Other studies indicate that oxidative stress, inflammation, vascular regression, and altered prostaglandin signalling may interact with androgen-driven mechanisms.

The review distinguishes between human clinical evidence, human hair-follicle and dermal papilla research, animal models, in-vitro experiments, molecular studies, and secondary literature. These evidence types are not treated as interchangeable. Findings from laboratory and animal models are presented as mechanistic or preclinical evidence and are not interpreted as equivalent to demonstrated clinical efficacy in humans.

The review also examines why DHT should not be considered the sole biological explanation for hair loss. The available literature supports a model in which androgen signalling acts within a wider network of follicular processes involving regenerative signalling, inflammatory pathways, oxidative stress, vascular changes, prostaglandins, and the regulation of follicular stem cells and dermal papilla activity.

This document is a narrative literature review and secondary research synthesis prepared by LUSTRAO(lustrao.com). It is not a new clinical trial and is not itself a peer-reviewed journal publication. No new human or animal data were collected for this review. The findings discussed are derived from previously published research and identified secondary literature.

The review is intended to provide a structured account of the biological pathways involved in hair growth and hair loss, together with the strengths and limitations of the available evidence.