Modulate Hair Growth Research Articles

Modulation of hair growth by topical drug delivery enhanced by STAR particles

Topical treatments to modulate hair growth are generally limited by low drug bioavailability due to poor skin permeability. Here, we studied the use of STAR particles, which are millimeter-sized ceramic particles with protruding microneedles, to form micropores in the skin to increase skin permeability to hair growth-modulating drugs. STAR particle design and fabrication were optimized, and the resulting STAR particles were shown to reduce lag time and increase skin permeability to minoxidil and acyclovir by more than three-fold compared to no treatment in pig skin ex vivo. In rats, STAR particles also improved topical delivery of minoxidil and acyclovir, which resulted in an increase or a decrease in the number, length and/or thickness of hairs and/or the number of anagen-phase hair follicles after minoxidil or acyclovir treatment, respectively. Clinical exam and histological evaluation showed no evidence of skin irritation or other adverse effects of the treatments. We conclude that STAR particles can increase topical delivery of minoxidil and acyclovir to improve modulation of hair growth promotion and inhibition, respectively.

562 Neuroendocrinology of human scalp hair follicles: Growth hormone-releasing hormone (GHRH) stimulates hair growth and controls a fully functional intrafollicular hypothalamic-pituitary-somatotropic (HPS) signaling axis

Human scalp hair follicles (HFs) are a major non-classical site of neurohormone production. While we had previously shown that growth hormone (GH), unexpectedly, inhibits female human scalp HFs growth ex vivo, it is unknown whether human HFs also produce key HPS axis neurohormones themselves, i.e. GH, its upstream regulator, GHRH, and/or the negative feedback control, somatostatin (SST), and whether GHRH modulates hair growth. To answer these questions, human scalp HFs were organ-cultured and stimulated with human GH (100 or 300ng/mL), GHRH (100 or 300ng/mL), or vehicle for mRNA or protein analysis of key HPS axis elements.

Hair Growth Promotion Effect of Nelumbinis Semen Extract with High Antioxidant Activity.

This study investigated the hair regeneration promotion and hair loss prevention properties of Nelumbinis Semen (NS) extract in vitro and in vivo. The effect of NS on the proliferation and migration of human dermal papilla cells (hDPCs) was measured in vitro via CCK-8 and scratch migration assays, after which the antioxidant activity of NS was also quantified. NS extracts were then applied to the back of 7-week-old C57BL/6 mice for 3 weeks to monitor hair growth patterns and hair follicle (HF) histology. The mice were divided into three groups: negative control group (NC; DMSO), positive control group (PC; 3% minoxidil), and experimental group (NS extract 1,000 ppm). Moreover, to study the molecular mechanisms by which NS extract regenerates hair growth, real-time PCR was used to analyze factors related to the hair growth cycle. The NS extracts were found to possess high antioxidant properties due to their high flavonoid contents and electron-donating ability. Moreover, NS extracts enhanced hDPC proliferation and migration in a concentration-dependent manner (15.63–125 ppm). The hair growth index and growth area of the NS group (2.81 score, 81%) on day 14 were higher than those of the PC group (2.65 score, 68%) (p < 0.05). Additionally, the HFs of the NS group were located deep in the subcutis, similar to the PC group with developed hair roots. Moreover, the mRNA expression of VEGF and IGF-1 was higher in the NS group compared to the PC group, whereas TGF-β1 expression was lower (p < 0.05). Our findings indicate that NS modulates hair growth by increasing IGF-1 and VEGF expression while inhibiting that of TGF-β1. Therefore, our findings suggest that NS extract is a promising new hair loss treatment derived from a natural substance that helps promote hair growth and prevent hair loss.

Compartmentalised metabolic programmes in human anagen hair follicles: New targets to modulate epithelial stem cell behaviour, keratinocyte proliferation and hair follicle immune status?

Human scalp hair follicles (HF) preferentially engage in glycolysis followed by lactate production in the presence of oxygen (i.e. the Warburg effect). Through the spatiotemporally controlled expression of key metabolic proteins, we hypothesise that the Warburg effect and other HF metabolic programmes are compartmentalised by region in order to regulate regional cell fate and phenotypes, such as epithelial stem cell quiescence in the bulge or keratinocyte proliferation in the hair matrix. We further propose that metabolic conditions in the HF are organised in accordance with the lactate shuttle, hypothesised to occur in other tissue systems and tumours, but never before described in the HF. Specifically, we argue that lactate is produced and exported by glycolytic GLUT1+ lower outer root sheath (ORS) keratinocytes. We further propose that lactate is then utilised by neighbouring highly proliferative matrix keratinocytes to fuel oxidative metabolism via MCT1-mediated uptake. Furthermore, as lactate has been described to be immunomodulatory, its production and accumulation could enhance immune tolerance in the HF bulb. Here we delineate how to experimentally probe this hypothesis, define major open questions and present preliminary immunohistological evidence in support of metabolic compartmentalisation and lactate shuttling. Overall, we argue that basic and translational hair research needs to rediscover the importance of lactate in human HF biology, well beyond its recognised role in murine HF epithelial stem cells, and should explore how HF metabolism can be therapeutically targeted to modulate hair growth and the immunological HF microenvironment as a novel strategy for managing hair loss disorders.

Androgenetic alopecia-associated cytokines

It is widely accepted that the occurrence of androgenetic alopecia (AGA) is closely related to androgen,androgen receptor and androgen-metabolizing enzymes.However,how they work in AGA remains unclear.Recent studies have shown that androgen exerts their roles by regulating various cytokines secreted by dermal papilla cells.At present,it is considered that insulin-like growth factor,vascular endothelial growth factor,transforming growth factor-β and Wnt inhibitory factor-1 are the most important and well-studied cytokines in the pathogenesis of AA,which may modulate hair growth via accelerating or deccelarating the growth of hair follicles. Key words: Alopecia; Androgen; Cytokines

6-Gingerol inhibits hair shaft growth in cultured human hair follicles and modulates hair growth in mice.

Ginger (Zingiber officinale) has been traditionally used to check hair loss and stimulate hair growth in East Asia. Several companies produce shampoo containing an extract of ginger claimed to have anti-hair loss and hair growth promotion properties. However, there is no scientific evidence to back up these claims. This study was undertaken to measure 6-gingerol, the main active component of ginger, on hair shaft elongation in vitro and hair growth in vivo, and to investigate its effect on human dermal papilla cells (DPCs) in vivo and in vitro. 6-Gingerol suppressed hair growth in hair follicles in culture and the proliferation of cultured DPCs. The growth inhibition of DPCs by 6-gingerol in vitro may reflect a decrease in the Bcl-2/Bax ratio. Similar results were obtained in vivo. The results of this study showed that 6-gingerol does not have the ability to promote hair growth, on the contrary, can suppress human hair growth via its inhibitory and pro-apoptotic effects on DPCs in vitro, and can cause prolongation of telogen phase in vivo. Thus, 6-gingerol rather than being a hair growth stimulating drug, it is a potential hair growth suppressive drug; i.e. for hair removal.

Hormonal changes in menopause: do they contribute to a ‘midlife hair crisis’ in women?

Female pattern hair loss is a common problem affecting a large number of women worldwide but beset by a paucity of research. The study of androgens has hitherto dominated the field of hair biology but there is increasing scientific and clinical data to suggest that nonandrogen signals can also affect the folliculosebaceous unit, especially in women. The discovery of oestrogen receptor beta has renewed and redefined prior concepts of oestrogen activity and signalling in hair biology. It is postulated that oestrogens modulate hair growth by their influence on a number of other hormones, growth factors, transcription factors and cytokines. The menopause is a period in which significant changes in oestrogen levels are recorded, and this review discusses studies that help to clarify the link between menopause and the perception of thinning hair. In a study of pre- and postmenopausal women without alopecia, menopausal status significantly influenced hair parameters, specifically hair growth rate, percentage anagen and hair diameter distributions, most notably in the frontal scalp. Hair density decreased with age, but was not correlated with menopausal status. Analyses of hair amount using a model of hair density and hair diameters suggest that the impact of changing hair parameters is most notable in the mid-forties for women.

Erythropoietin promotes hair shaft growth in cultured human hair follicles and modulates hair growth in mice

Recent studies have shown that erythropoietin (EPO)/erythropoietin receptor (EPOR) signaling exist in both human and mouse hair follicles (HFs). To investigate whether dermal papilla cells (DPCs) express functional EPOR and, if so, to investigate effects of EPO on hair shaft growth in cultured human scalp hair follicles and hair growth in mice. EPOR expression in DPCs and follicular keratinocytes was examined by RT-PCR and immunoblot. Phosphorylation of EPOR signaling pathway mediators by EPO treatment was examined by immunoblot. MTT assay was employed to check cell viability after EPO treatment. Hair shaft growth was measured in the absence or presence of EPO and matrix keratinocyte proliferation was examined by Ki-67 immunostaining in cultured hair follicles. Agarose beads containing EPO were implanted into dorsal skin of C57BL/6 mice to examine effects of EPO on hair growth in vivo. EPOR mRNA and protein are expressed in cultured human DPCs. EPOR signaling pathway mediators such as EPOR and Akt are phosphorylated by EPO in DPCs. EPO significantly promoted the growth of DPCs and elongated hair shafts with increased proliferation of matrix keratinocytes in cultured human hair follicles. In addition, EPO not only promoted anagen induction from telogen but also prolonged anagen phase. EPO may modulate hair growth by stimulating DPCs that express functional EPOR.

Melatonin and the hair follicle

Melatonin, the chief secretory product of the pineal gland, has long been known to modulate hair growth, pigmentation and/or molting in many species, presumably as a key neuroendocrine regulator that couples coat phenotype and function to photoperiod-dependent environmental and reproductive changes. However, the detailed effects and mechanisms of this surprisingly pleiotropic indole on the hair follicle (HF) regarding growth control and pigmentation have not yet been completely understood. While unspecific melatonin binding sites have long been identified (e.g., in goat and mouse HFs), specific melatonin membrane MT2 receptor transcripts and both protein and mRNA expression for a specific nuclear melatonin binding site [retinoid-related orphan receptor alpha (RORalpha)] have only recently been identified in murine HFs. MT1, known to be expressed in human skin cells, is not transcribed in mouse skin. After initial enzymologic data from hamster skin related to potential intracutaneous melatonin synthesis, it has recently been demonstrated that murine and human skin, namely human scalp HFs in anagen, are important sites of extrapineal melatonin synthesis. Moreover, HF melatonin production is enhanced by catecholamines (as it classically occurs in the pineal gland). Melatonin may also functionally play a role in hair-cycle control, as it down-regulates both apoptosis and estrogen receptor-alpha expression, and modulates MT2 and RORalpha expression in murine skin in a hair-cycle-dependent manner. Because of melatonin's additional potency as a free radical scavenger and DNA repair inducer, the metabolically and proliferatively highly active anagen hair bulb may also exploit melatonin synthesis in loco as a self-cytoprotective strategy.