|Year : 2012 | Volume
| Issue : 3 | Page : 154-157
Miniaturized hairs maintain contact with the arrector pili muscle in alopecia areata but not in androgenetic alopecia: A model for reversible miniaturization and potential for hair regrowth
Anousha Yazdabadi1, D Whiting2, NW Rufaut1, R Sinclair1
1 Department of Dermatology; Medicine, (SVHM), The University of Melbourne, St Vincent's Hospital, Fitzroy, VIC, Australia
2 The Hair and Skin Research and Treatment Centre, Dallas, Texas, USA
|Date of Web Publication||24-Aug-2012|
Department of Dermatology, St. Vincent's Hospital Melbourne, 41 Victoria Parade Fitzroy VIC 3065
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Hair follicle miniaturization is the hallmark of male pattern hair loss (MPHL), female pattern hair loss (FPHL), and alopecia areata (AA). AA has the potential for complete hair regrowth and reversal of miniaturization. MPHL and FPHL are either irreversible or show only partial regrowth and minimal reversal of miniaturization. Hypothesis: The arrector pili muscle (APM) attachment to the hair follicle bulge, a recognized repository of stem cells may be necessary for reversal of hair follicle miniaturization. Materials and Methods: Sequential histological sections from MPHL, FPHL, AA, and telogen effluvium were used to create three-dimensional images to compare the relationship between the APM and bulge. Results: In AA, contact was maintained between the APM and the bulge of miniaturized follicles while in MPHL and FPHL contact was lost. Discussion: Contact between the APM and the bulge in AA may be required for reversal of hair follicle miniaturization. Maintenance of contact between miniaturized follicles in AA could explain the complete hair regrowth while loss of contact between the APM and the bulge in MPHL and FPHL may explain why the hair loss is largely irreversible. This loss of contact may reflect changes in stem cell biology that also underlie irreversible miniaturization.
Keywords: Arrector pili muscle, follicle, hair, regrowth
|How to cite this article:|
Yazdabadi A, Whiting D, Rufaut N W, Sinclair R. Miniaturized hairs maintain contact with the arrector pili muscle in alopecia areata but not in androgenetic alopecia: A model for reversible miniaturization and potential for hair regrowth. Int J Trichol 2012;4:154-7
|How to cite this URL:|
Yazdabadi A, Whiting D, Rufaut N W, Sinclair R. Miniaturized hairs maintain contact with the arrector pili muscle in alopecia areata but not in androgenetic alopecia: A model for reversible miniaturization and potential for hair regrowth. Int J Trichol [serial online] 2012 [cited 2019 Nov 12];4:154-7. Available from: http://www.ijtrichology.com/text.asp?2012/4/3/154/100069
| Introduction|| |
Hair follicles are dynamic. Vellus to terminal transformation and vice versa occurs physiologically.  Terminal to vellus transformation leading to hair follicle miniaturization occurs pathologically in male and female patterned hair loss (FPHL), alopecia areata (AA), secondary syphilis, and traction alopecia.
Hair follicle miniaturization has been extensively studied in the context of male pattern hair loss (MPHL). The relationship between hair cortex diameter, hair matrix size, and volume of the dermal papilla is well described, , and disruption of this relationship may result in follicle miniaturization. 
One of the most striking features of MPHL and FPHL is the highly reproducible pattern of hair loss which on a large scale affects certain zones of the scalp preferentially and on a smaller scale hairs within follicular units (FU) are preferentially affected resulting in FUs normally containing 3-5 terminal hairs being reduced to 1-2 terminal hairs and 2-3 vellus hairs. 
FU are collections of 3-5 hairs surrounded by a fibrous connective tissue sheath, served by a single arrector pili muscle (APM) [Figure 1]. , The hairs often emerge on the scalp through a single pore. Montagna and Carlisle observed these on freeze fracture images of the under surface of 6-month-old human fetal scalp.  He described primary and secondary follicles; however, the follicular structures seen on the adult scalp most likely represent compound primary follicles like those seen in the possum, rabbit, and lemur, rather than true secondary follicles as described in sheep. These compound primary follicles are not to be confused with Meijere's trio groups of primary follicles that cycle in phase. 
|Figure 1: The follicular unit; composed of 2-3 terminal follicles, 1-2 vellus follicles, a sebaceous gland, and an arborising APM (H and E 40×)|
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AA also results in follicular miniaturization.  However, in contrast to androgenetic alopecia which is of gradual onset and at best only partially reversible, AA has an abrupt onset, is unpredictable, has no specific pattern, and is completely reversed with successful treatment. 
The APM attaches to the outer root sheath (ORS) of the follicle at the level of the bulge at the trochanter. ,, The bulge is the main repository of epithelial stem cells and inflammation at the bulge is the hallmark of primary cicatricial alopecia.  The APM in human beings is thought to be vestigial in nature but recent evidence shows that the APM attaches to all the follicles within an FU. , However, interactions between the APM and the bulge as a correlate of follicle miniaturization have not been investigated.
We were interested in whether there were anatomical differences in the miniaturized follicles that might predict reversibility of miniaturization and in particular whether contact between the bulge and the APM is required in order to reverse miniaturization. In testing this hypothesis, we compared APM attachment in AA, where follicle miniaturization is reversible, with MPHL and FPHL where hair follicle miniaturization is either irreversible or only partially reversible.
| Materials and Methods|| |
Four millimeter scalp punch biopsies were taken from patients with MPHL, FPHL, AA, and chronic telogen effluvium (CTE) as part of their routine care. As scalp biopsies from normal hair are difficult to attain, CTE was used as the control. Histology of CTE is similar to normal scalp. Although in CTE, the anagen to telogen ratio is 8 : 1 compared with 14 : 1 in normal scalp, the total number of hairs and the T : V hair ratio (mean, 8 : 1) resembles that of normal scalp.  Biopsies were horizontally sectioned and stained with Mason's Trichrome to distinguish the red-staining APM from the surrounding blue collagen. An Optronics Camera was used to take digital photograph of each section and saved in JPEG format.
Using the Reconstruct software, as developed by J. C. Fiala and K. M. Harris at Boston University, MA, USA (http://synapses.mcg.edu/tools/index.stm), the sequential sections were aligned manually using three points on fixed structures of successive sections.  Each hair follicle was then individually traced and arbitrarily allocated a green color. Next, the surrounding APM was traced on each successive section. Where there was a cluster of closely aligned muscle fibers associated with an FU, a single line was used to join them. The AP was allocated a blue color. The Boissonnat surface was then selected to generate a three-dimensional view. Comparison was made between three-dimensional reconstructions of the follicles and the APM of the four different hair loss entities.
| Results|| |
In AA, all miniaturized follicles within a FU maintained contact with the APM. In MPHL, all the follicles within the FU were miniaturized and a uniform loss of contact between the APM and bulge was demonstrated. In FPHL where individual FU demonstrated heterogeneity in miniaturization, the follicle closest to the insertion of the APM appears to be the most resistant to miniaturization. This follicle had the largest surface area of attachment to the APM. Residual terminal hair follicles generally maintained contact with the APM, but adjacent miniaturized follicles within the FU lost contact between the APM and the bulge. In CTE, there was no hair follicle miniaturization and all the APM demonstrated the most intimate attachment with the most proximal hair follicles and lesser degrees of attachment with the more distal follicles [Table 1].
|Table 1: Summary of the proportion of hair follicles maintaining contact with the arrector pili muscle|
Click here to view
| Discussion|| |
In MPHL and FPHL, where follicle miniaturization is either irreversible or only partially reversible, there was a consistent loss of attachment of the APM to vellus hair follicles. This was in contrast to potentially reversible AA, in which the APM maintained contact with the ORS of the miniaturized secondary vellus follicles [Figure 2].
|Figure 2: Three-dimensional reconstructions of AA (a) and FPHL (b) demonstrating the loss of contact of the APM with the ORS of the vellus hair follicle in FPHL which is largely irreversible compared with maintenance of this contact of the APM with ORS in AA which is potentially completely reversible|
Click here to view
Song et al., in their three-dimensional reconstruction of the FU, demonstrated that the APM attached to all the hair follicles within the FU, with tightest attachment to one follicle in particular.  In our reconstructions of CTE, we demonstrate a similar phenomenon. Furthermore, in FPHL, we found that the persisting terminal hairs largely maintain contact between the AP and the ORS.
The concept of primary and secondary hair follicles in sheep and compound primary follicles in some mammals is well described. Despite the work of Montagna, this concept has not received much attention in human beings. We have previously postulated that in FPHL, there is a hierarchy of androgen responsiveness within FU, with preferential miniaturization of secondary follicles.  Thus, the primary follicles may be those with the most intimate association with the AP, as well as the least susceptibility to miniaturization. The more susceptible secondary follicles may be those with less intimate contact with the APM.
The loss of intimate interaction between the APM and the follicle in irreversible hair loss is unlikely to be coincidental and several hypotheses may account for this phenomenon. It may be that the APM serves as a source of stem cells to help maintain the follicle. Perhaps more likely, the APM support or stimulate stem cell populations in the bulge or dermal sheath, via as yet uncharacterized biochemical or mechanical mechanisms. Loss of contact with the APM would then induce miniaturization by disrupting the function of stem cells resident in the follicle itself. Finally, the regression of the APM may be the result of a disease process that disrupts a stem cell population which maintains the APM as well as the follicle. Notably, follicular stem cell populations have been shown to undergo smooth muscle or skeletal muscle differentiation in vitro. 
In conclusion, we have identified loss of contact between the APM and the ORS in miniaturized hairs in MPHL and FPHL. In FPHL, the persisting terminal hair maintains contact with the APM. In contrast, all the miniaturized hairs in AA maintain contact with the APM. We propose that the persisting contact between the APM and ORS predicts reversibility of miniaturization.
In addition, we propose that in FPHL, where there is a hierarchy of androgen sensitivity within FUs, the persisting terminal hairs represent primary follicle within the FU and that the miniaturized follicles that lose contact with the AP represent the secondary follicles.
It remains unclear whether APM regression is a cause or effect of permanent follicle miniaturization and further studies are required to characterize the role of APM regression in the etiology of hair growth disorders.
| Acknowledgments|| |
Support: Viola Edith Reid Scholarship, University of Melbourne, St. Vincent's Hospital Research Endowment Fund Scholarship
| References|| |
|1.||Sinclair R, Banfield C, Dawber R. Handbook of diseases of the hair and scalp. Oxford: Blackwell Science; 1999. |
|2.||Van Scott EJ, Ekel TM. Geometric relationships between the matrix of the hair bulb and its dermal papilla in normal and alopecic scalp. J Invest Dermatol 1958;31:281-7. |
|3.||Elliott K, Stephenson TJ, Messenger AG. Differences in hair follicle dermal papilla volume are due to extracellular matrix volume and cell number: Implications for the control of hair follicle size and androgen responses. J Invest Dermatol 1999;113:873-7. |
|4.||Jahoda CA. Cellular and developmental aspects of androgenetic alopecia. Exp Dermatol 1998;7:235-48. |
|5.||Yazdabadi A, Magee J, Harrison S, Sinclair R. The Ludwig pattern of androgenetic alopecia is due to a hierarchy of androgen sensitivity within follicular units that leads to selective miniaturization and a reduction in the number of terminal hairs per follicular unit. Br J Dermatol 2008;159:1300-2. |
|6.||Headington JT. Transverse microscopic anatomy of the human scalp. A basis for a morphometric approach to disorders of the hair follicle. Arch Dermatol 1984;120:449-56. |
|7.||Song WC, Hwang WJ, Shin C, Koh KS. A new model for the morphology of the arrector pili muscle in the follicular unit based on three-dimensional reconstruction. J Anat 2006;208:643-8. |
|8.||Montagna WKA, Carlisle KS. Atlas of Normal Human Skin. Berlin: Springer-Verlag; 1992. |
|9.||Saitoh M, Uzuka M, Sakamoto M. Human hair cycle. J Invest Dermatol 1970;54:65-81. |
|10.||Whiting DA. Histopathologic features of alopecia areata: A new look. Arch Dermatol 2003;139:1555-9. |
|11.||Messenger A. Alopecia Areata. In: Burns TBS, Cox N, Griffiths C, editors. Rook's textbook of Dermatology. 2004. |
|12.||Poblet E, Jimenez F, Ortega F. The contribution of the arrector pili muscle and sebaceous glands to the follicular unit structure. J Am Acad Dermatol 2004;51:217-22. |
|13.||Tiede S, Kloepper JE, Whiting DA, Paus R. The 'follicular trochanter': An epithelial compartment of the human hair follicle bulge region in need of further characterization. Br J Dermatol 2007;157:1013-6. |
|14.||Cotsarelis G. Epithelial stem cells: A folliculocentric view. J Invest Dermatol 2006;126:1459-68. |
|15.||Harrison S, Sinclair R. Telogen effluvium. Clin Exp Dermatol 2002;27:389-5. |
|16.||Fiala JC. Reconstruct: A free editor for serial section microscopy. J Microsc 2005;218(Pt 1):52-61. |
|17.||Liu JY, Peng HF, Andreadis ST. Contractile smooth muscle cells derived from hair-follicle stem cells. Cardiovasc Res 2008;79:24-33. |
[Figure 1], [Figure 2]