Interaction of Minoxidil with Pigment in Cells of the Hair Follicle: An Example of Binding without Apparent Biological Effects

Buhl, Allen E.; Kawabe, Thomas T.; MacCallum, Donald K.; Waldon, Daniel J.; Knight, Karen A.; Johnson, George

doi:10.1159/000211028

Cited by 7 publications

(3 citation statements)

References 10 publications

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“…However, we showed that millimolar concentrations of Minoxidil are partially cy totoxic, in agreement with other reports [13][14][15]17], rendering this pro-differentiative ef fect difficult to interpret. On an other hand, such high concentrations are poorly relevant to in vivo data (maximal plasmatic levels of Minoxidil after systemic administration of hair growth-promoting doses: 0.775 \iM), but we cannot exclude an accumulation of drug in some compartments of the follicle, especially the hair shaft rich in keratins and melanin [42]. Such an accumulation in the hair shaft could more probably occur after topical Mi noxidil treatment: we can so far speculate that millimolar doses of Minoxidil could be present in close proximity to the keratogenous zone, thus favoring keratinocyte differentia tion and resulting in hair shaft thickening.…”

Section: Minoxidil On Nhk Prolifcration/differentiationmentioning

confidence: 92%

Biphasic Effects of Minoxidil on the Proliferation and Differentiation of Normal Human Keratinocytes

Boyera

Galey

Bernard³

1997

Skin Pharmacol Physiol

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Minoxidil is the most used drug with proved effects in the treatment of androgenetic alopecia (AGA), but little is known about its pharmacological activity and target cells in hair follicles. As AGA is characterized by follicle atrophy, accelerated hair cycles and hair fiber thinning, we postulated that kerati-nocyte proliferation/differentiation is affected and we tested Minoxidil’s effects on those parameters. Normal human keratinocytes (NHK) of follicular or epidermal origin were cultured in the presence of Minoxidil (0, 0.1, 1, 10, 100, 1,000 μM) during 5-8 days in various media (high-/low-calcium content, with or without serum). Proliferation was assessed by mitochondrial dehydrogenase activity (XTT), BrdU incorporation, lysosome numeration (neutral red incorporation) and total protein dosage. Drug-induced cytotoxicity was measured by lactate dehydrogenase release in culture supernatant, and pro-differentiating effects were evaluated by relative involucrin expression (ELISA dosage). On this basis, we showed that Minoxidil had biphasic effects on the proliferation and differentiation of NHK: Minoxidil stimulated NHK proliferation at micromolar doses, while antiproliferative, pro-differentiative and partially cyto-toxic effects were observed with millimolar concentrations. We can hypothesize that Minoxidil hypertrichotic activity in vivo is possibly mediated by the maintenance of proliferative potential in follicular keratinocytes precociously committed to differentiation.

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Section: Minoxidil On Nhk Prolifcration/differentiationmentioning

confidence: 92%

Biphasic Effects of Minoxidil on the Proliferation and Differentiation of Normal Human Keratinocytes

Boyera

Galey

Bernard³

1997

Skin Pharmacol Physiol

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“…Uptake studies in mouse vibrissae follicles showed that minoxidil and minoxidil sulphate concentrated in melanocytes and pigmented epithelial cells in the suprapapillary region of the follicle. However, this was probably due to nonspecific binding to melanin as there was no evidence of minoxidil binding in nonpigmented follicles yet pigmented and nonpigmented follicles showed a similar growth response to minoxidil 43 …”

Section: The Cellular Response To Minoxidilmentioning

confidence: 96%

Minoxidil: mechanisms of action on hair growth

Messenger¹,

Rundegren²

2004

Br J Dermatol

504

368

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We have known for over 30 years that minoxidil stimulates hair growth, yet our understanding of its mechanism of action on the hair follicle is very limited. In animal studies, topical minoxidil shortens telogen, causing premature entry of resting hair follicles into anagen, and it probably has a similar action in humans. Minoxidil may also cause prolongation of anagen and increases hair follicle size. Orally administered minoxidil lowers blood pressure by relaxing vascular smooth muscle through the action of its sulphated metabolite, minoxidil sulphate, as an opener of sarcolemmal KATP channels. There is some evidence that the stimulatory effect of minoxidil on hair growth is also due to the opening of potassium channels by minoxidil sulphate, but this idea has been difficult to prove and to date there has been no clear demonstration that KATP channels are expressed in the hair follicle. A number of in vitro effects of minoxidil have been described in monocultures of various skin and hair follicle cell types including stimulation of cell proliferation, inhibition of collagen synthesis, and stimulation of vascular endothelial growth factor and prostaglandin synthesis. Some or all of these effects may be relevant to hair growth, but the application of results obtained in cell culture studies to the complex biology of the hair follicle is uncertain. In this article we review the current state of knowledge on the mode of action of minoxidil on hair growth and indicate lines of future research.

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“…With haloperidol, ofloxacin and methadone the measured concentrations were higher in pigmented than in non-pigmented hair [5,77,78,87]. Buhl et al [14] demonstrated the uptake of a radio-labelled drug by autoradiography and found an accumulation in the differentiating matrix cells superior to the dermal papilla with a distribution similar to that of pigment. Drug uptake was significantly less in unpigmented follicles.…”

Section: Principles Of Biological Transport Across Membranes Applied mentioning

confidence: 99%

A discourse on human hair fibers and reflections on the conservation of drug molecules

Pötsch

1996

Int J Leg Med

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A gross discourse on human hair fibers and their formation is presented stressing the various interdisciplinary aspects, such as the morphological, biological, structural and biochemical data considered to be important in the field of hair analysis. An attempt is made to explain the incorporation of drug molecules during hair fiber formation by using the classical concepts of drug absorption based on lipoid theory and the pH-partition hypothesis as well as a modern biological approach on the permeability of cell membranes. In addition to the physiochemical considerations of the transport properties of a particular drug molecule such as a) the lipophilicity, which determines permeability through the membrane, b) the pKa value, c) the plasma protein binding and d) the molecular size and shape of the drug molecule, drug absorption is thought to be limited by the surface area and the residence time in the hair bulb. The thermodynamic approach according to the Kedem-Katchalsky equations seems even more satisfying. When the principles of biological transport across cell membranes are applied to the cell populations present in the hair root, a hypothesis of extracellular and intracellular drug localizations results. It is speculated that the cell membrane complex (CMC) and the melanin granules present the main sources of incorporated drug molecules within the keratinized hair fibers.

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Interaction of Minoxidil with Pigment in Cells of the Hair Follicle: An Example of Binding without Apparent Biological Effects

Cited by 7 publications

References 10 publications

Biphasic Effects of Minoxidil on the Proliferation and Differentiation of Normal Human Keratinocytes

Biphasic Effects of Minoxidil on the Proliferation and Differentiation of Normal Human Keratinocytes

Minoxidil: mechanisms of action on hair growth

A discourse on human hair fibers and reflections on the conservation of drug molecules

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