Minoxidil Stimulates Mouse Vibrissae Follicles in Organ Culture

Buhl, Allen E.; Waldon, Daniel J.; Kawabe, Thomas T.; Holland, James M.

doi:10.1111/1523-1747.ep12277095

Cited by 131 publications

(71 citation statements)

References 12 publications

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“…25) Buhl et al reported that minoxidil stimulates hair growth of mouse vibrissae follicles in organ culture. 26) In a whole skin piece culture system from 4-week-old mice, 27) it also demonstrated that minoxidil promoted hair follicle elongation. Minoxidil causes telogen hair follicles to enter the anagen phase, and prolongs the anagen period, and thus increases hair follicle size.…”

Section: Discussionmentioning

confidence: 95%

The Additive Effects of Minoxidil and Retinol on Human Hair Growth in Vitro

Yoo

Chang

Pyo

et al. 2007

Biological & Pharmaceutical Bulletin

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Minoxidil, a pyrimidine derivative (2,4-diamino-6-piperidino-pyrimidine-3-oxide) is an adenosine triphosphate (ATP) sensitive potassium chennel (K ATP chennel) opener, and is the most commonly used drug for the treatment of androgenetic alopecia.1) Topical minoxidil shortens the telogen phase by induction of the entry of resting hair follicles into the anagen phase, prolongs anagen growth phase and increases the volume of hair follicles. Although the mechanism through which minoxidil promotes hair growth is still speculative, a number of in vitro studies using minoxidil have been described in various skin and hair follicle cell types including the stimulation of cell proliferation, and the induction of vascular endothelial growth factor 2,3) and prostaglandin synthesis.4) In addition, minoxidil has been shown to increase blood circulation around hair follicles 5,6) and to markedly elevate 17b-hydroxysteroid dehydrogenase activity, which accelerated the conversion of testosterone to weaker androgens. 7)Retinol significantly improves the scalp skin condition and promotes hair growth, in terms of the keratinization of skin and hair. 8) Retinol is ingested in precursor forms; animal sources contain retinyl esters whereas plants contain carotenoids. Tissue cells convert these organic precursor forms to retinol, and this to either retinal or retinoic acid. These two species exert profound effects on the growth, maturation, and differentiation of many cell types, both in vivo and in vitro.8) Retinoic acid, the active metabolite of vitamin A, has been reported to play an important role in the growth, differentiation and maintenance of hair follicles. 9) Moreover, cellular retinoic acid-binding proteins (CRBPs) are known to be important for the mediations of some of the effects of retinoids. These effects are mediated by two classes of nuclear retinoic acid receptors, termed retinoic acid receptor (RAR) and retinoid x receptor (RXR), and each of these classes is composed of subtypes designated alpha, beta, and gamma.Recently, we showed that minoxidil prolongs the anagen stage and that the enhanced hair growth may result from two mechanisms: (i) the activations of Erk and Akt signaling which enhance the survival of cultured DPCs, and (ii) an increase in the Bcl-2/Bax ratio which protects cells against cell death.10) The aim of the present study was to evaluate possible additive interaction between minoxidil and retinol on human hair growth and to investigate the mechanism of action of minoxidil plus retinol using cultured human DPCs and keratinocytes. MATERIALS AND METHODS MaterialsMinoxidil and retinol were purchased from Sigma (St Louis, MO, U.S.A.). Minoxidil was dissolved in 0.12 mM HCl and a 1.0 mM minoxidil stock solution was stored at Ϫ20°C. Retinol was dissolved in absolute ethanol and shielded from the light using aluminum foil until required. All inhibitors [U0126, an ERK kinase (MEK1 and 2)-inhibitor; LY 294002 (LY) and Wortmannin, selective PI3K inhibitor] were purchased from Calbiochem (San Diego, CA, U.S.A.)...

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Section: Discussionmentioning

confidence: 95%

The Additive Effects of Minoxidil and Retinol on Human Hair Growth in Vitro

Yoo

Chang

Pyo

et al. 2007

Biological & Pharmaceutical Bulletin

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“…The hair follicle culture method has several advantages in hair research, including the measure of hair-fiber elongation and maintenance of normal architecture. 39,40) In this study, we isolated rat vibrissa follicles from 23-d old rats and found that the S. muticum extract significantly promoted hair-fiber length in cultured rat vibrissa follicles. By the way, we couldn't find the dose-dependency of the S. muticum extract on the elongation of hair-fiber length.…”

Section: Discussionmentioning

confidence: 87%

“…To identify new hair-growing agents, cultures of hair fol- licles from several species such as human, 11,32) rat, 39) sheep 51) and mouse 40,52) were developed. The hair follicle culture method has several advantages in hair research, including the measure of hair-fiber elongation and maintenance of normal architecture.…”

Section: Discussionmentioning

confidence: 99%

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Promotion Effect of Apo-9′-fucoxanthinone from <i>Sargassum muticum</i> on Hair Growth <i>via</i> the Activation of Wnt/β-Catenin and VEGF-R2

Kang

Yoo

Hyun

et al. 2016

Biological & Pharmaceutical Bulletin

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This study was conducted to evaluate the effects of Sargassum muticum extract and apo-9′-fucoxanthinone, a principal component of S. muticum, on hair growth. When rat vibrissa follicles were treated with S. muticum extract for 21 d, the hair-fiber lengths for the vibrissa follicles increased significantly. Treatment with the S. muticum extract and the EtOAc fraction of the S. muticum extract markedly increased the proliferation of dermal papilla cells (DPCs) and decreased the 5α-reductase activity. In addition, the EtOAc fraction of the S. muticum extract significantly promoted anagen initiation in C57BL/6 mice. Especially, apo-9′-fucoxanthinone, an active constituent from the S. muticum extract, caused an increase in DPC proliferation and a decrease in 5α-reductase activity. To elucidate the molecular mechanisms of apo-9′-fucoxanthinone on the proliferation of DPCs, we examined the level of various signaling proteins. Apo-9′-fucoxanthinone increased the level of vascular endothelial growth factor receptor-2 (VEGF-R2), Wnt/β-catenin signaling proteins such as phospho(ser9)-glycogen synthase kinase-3β (GSK-3β) and phospho(ser552)-β-catenin, whereas apo-9′-fucoxanthinone did not affect the transforming growth factor-β (TGF-β) signaling proteins such as Smad2/3. These results suggest that apo-9′-fucoxanthinone from S. muticum could have the potential for hair growth with DPC proliferation via the activation of Wnt/β-catenin signaling and the VEGF-R2 pathway.

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“…For this reason, the utility o f this human follicle culture system for pharmacological studies is unclear. In contrast, Buhl et al [12] have shown that minoxidil stimulates both DNA and protein synthesis in mouse whisker follicles in organ culture. We extended this finding to show that pinacidil and diazoxide, potassium channel openers whose therapeutic use has also been associated with hypertricho sis, also stimulate DNA synthesis in this mouse follicle culture system [ 13], These find ings thus support the utility o f cultured mouse whisker follicles as a model for testing com pounds for potential hypertrichotic activity.…”

Section: Introductionmentioning

confidence: 83%

Bisindolylmaleimide Protein-Kinase-C Inhibitors Delay the Decline in DNA Synthesis in Mouse Hair Follicle Organ Cultures

Harmon¹,

Nevins²,

Ducote³

et al. 1997

Skin Pharmacol Physiol

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We have used a series of bisindolylmaleimide selective pro-tein-kinase C (PKC) inhibitors to investigate the role of this enzyme in the regulation of cell proliferation in mouse hair follicle organ cultures. Mouse whisker follicles were isolated by microdissection, and rates of DNA synthesis during culture were determined from ³H-thymidine incorporation. The bis-indolylmaleimides Ro 31-7549, Ro 31-8161, Ro 31-8425 and Ro 31-8830 inhibit isolated brain PKC with IC₅₀ values of 8-80 nM, are > 60-fold less potent against protein kinase A, and inhibit PKC-mediated protein phosphorylation in platelets with IC₅₀ values in the range 0.25-4.4 μM. These PKC inhibitors were found to increase levels of mouse hair follicle DNA synthesis, with EC₅₀ values in the range 1-4 μM and maximal levels in the range 151-197% of control. Ro 31-7549 had an IC₅₀ value 50-fold lower than that of minoxidil, while the maximal level of DNA synthesis for the PKC inhibitor was 86% higher. Incubation of mouse hair follicles with Ro 31-7549 resulted in a delay of approximately 24 h in the onset of decline in follicular DNA synthesis rates. Ro 31-6045 and Ro 31-7208, bisindolylmaleimides without activity in the platelet PKC assay, did not affect mouse hair follicle DNA synthesis rates. Taken together, these findings show that PKC mediates, at least in part, the rapid loss of proliferative activity that occurs in mouse whisker follicles in culture, and provide further evidence that PKC plays a role as a negative proliferative signal in hair follicles.

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Minoxidil Stimulates Mouse Vibrissae Follicles in Organ Culture

Cited by 131 publications

References 12 publications

The Additive Effects of Minoxidil and Retinol on Human Hair Growth in Vitro

The Additive Effects of Minoxidil and Retinol on Human Hair Growth in Vitro

Promotion Effect of Apo-9′-fucoxanthinone from <i>Sargassum muticum</i> on Hair Growth <i>via</i> the Activation of Wnt/β-Catenin and VEGF-R2

Bisindolylmaleimide Protein-Kinase-C Inhibitors Delay the Decline in DNA Synthesis in Mouse Hair Follicle Organ Cultures

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