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Endocrinology Vol. 138, No. 1 356-361
Copyright © 1997 by The Endocrine Society

ARTICLES

Inhibition of Hair Growth by Testosterone in the Presence of Dermal Papilla Cells from the Frontal Bald Scalp of the Postpubertal Stumptailed Macaque1

Noriko Obana, Chawnshang Chang and Hideo Uno

Regional Primate Research Center, University of Wisconsin, Madison, Wisconsin 53715-1299

Address all correspondence and requests for reprints to: Hideo Uno, M.D., Ph.D., Regional Primate Research Center, 1223 Capitol Court, University of Wisconsin, Madison, Wisconsin 53715-1299.


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Hair-follicle regression in the bald scalps of stumptailed macaques develops after puberty, which corresponds to an elevation of serum testosterone and dihydrotestosterone. Using the cultured cells from the pre- and postpubertal macaques, we examined the role of dermal papilla cells in testosterone-induced inhibition of outer root sheath cell proliferation. Testosterone showed no effects on proliferation of either dermal papilla cells or outer root sheath cells cultured alone. Testosterone-induced inhibition of outer root sheath cell proliferation occurred only in coculture with dermal papilla cells derived from the bald scalps of adult macaques but not with dermal papilla cells from the hairy occipital scalps of adult macaques or the prebald frontal scalps of juvenile macaques. Furthermore, RU 58841, an androgen receptor blocker, antagonized this testosterone-elicited inhibition. Together our data indicate that the inhibitory effect of testosterone on proliferation of epithelial cells is age dependent, and androgen may play an essential role in hair growth either by inducing repressor(s) from dermal papilla cells, which may then inhibit the growth of epithelial cells of the hair follicle, or by inducing growth factor(s) from dermal papilla cells, which, in turn, may trigger the induction of some repressors in epithelial cells, thereby inhibiting the epithelial cell growth. Our animal studies also showed that RU 58841 has a dramatic effect on hair regrowth in the bald frontal scalp of the stumptailed macaque, which may further support our in vitro culture studies showing that antiandrogens can antagonize testosterone-elicited hair growth. In summary, our studies may provide a model for further isolation of androgen-regulated repressor(s)/growth factors, which may help control hair growth and baldness.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
IN 1969, Oliver demonstrated that interaction of the dermal papilla cells on follicular epithelial differentiation is probably of the same nature as embryonic induction, continuing throughout life and maintaining the functional integrity of adult follicles (1). Later, his colleagues demonstrated an inductive capacity of cultured dermal papilla cells implanted as pellets into the base of follicles from which the lower halves had been removed (2). Yuspa et al. (3) demonstrated that dermal papilla cells have the ability to stimulate hair growth in grafts of follicular buds on nude mice. Furthermore, the mechanism of androgens on secondary hairs suggests that the dermal papilla cells derived from the beard-hair follicle play an important role in stimulatory actions of androgens (4, 5, 6). The activities of 5{alpha}-reductase are higher in cultured beard dermal papilla cells than in cells from the occipital scalp (7). Similarly, dihydrotestosterone is known as a potent androgen for secondary hair growth as well as postpubertal growth of the prostate (8). Depending on their sites, androgens have paradoxically different effects on human hair follicles. Androgens stimulate hair growth in many sites, such as the beard and pubic areas but can cause hair regression on the scalp in genetically disposed individuals (9). The inhibitory actions of androgens using cultured dermal papilla cells derived from bald scalps have not been examined.

In human androgenetic alopecia, postpubertal elevation of testosterone seems to cause irreversible regression of hair follicles; prepubertal castration is known to prevent this androgenetic alopecia (10). The alopecia in frontal scalps of postpubertal stumptailed macaques manifests a progressive follicular regression similar to human androgenetic alopecia, and treatments with antiandrogen drugs can prevent or reverse this epigenetic alopecia (11, 12, 13, 14, 15).

In this study, we demonstrate testosterone-induced inhibition of proliferation of outer root sheath cells cocultured with dermal papilla cells derived from the bald frontal scalps of postpubertal macaques. We also examine the role of dermal papilla cells derived from the prebald frontal scalps of prepubertal macaques in testosterone-dependent inhibition of outer root sheath cell proliferation.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Animal subjects
Subject animals were male and female stumptailed macaques (Macaca arctoides), in the prepubertal (2 yr old, n = 3) and postpubertal stage (5–15 yr old, n = 16). Each animal was housed in our animal care facility (accredited by the American Association for Accreditation of Laboratory Animal Care).

Isolation and culture of dermal papilla cells and outer root sheath cells
Under anesthesia with ketamine hydrochloride (20 mg/kg, im), frontal and occipital scalp samples were obtained from pre- and postpubertal macaques using a 4-mm punch.

Dermal papillae were isolated from anagen hair follicles according to a recently reported method (16). Because the dermal papillae from juvenile prebald and adult bald frontal scalp skins were smaller than those from the occipital scalp skin of adult macaques (Fig. 1Go), the dermal papillae were isolated under a stereomicroscope at high magnification (x180) and carefully collected by micropipette. Lengths of each dermal papilla from the dome, which is attached to the hair matrix, to the base of the dermal papilla from frontal and occipital scalps of pre- and postpubertal macaques were determined by taking photographs under a light microscope. The bald and prebald dermal papillae were transferred and cultured with DMEM supplemented with 10% charcoal-treated FBS (Sigma, St. Louis, MO), penicillin (100 U/ml), and streptomycin (100 µg/ml). The dermal papillae explants attached to the plastic substrate within 7 days. Cells were subcultured after 0.1% trypsin treatment (usually 4 weeks after the beginning of primary cell cultures). The dermal papillae from the hairy occipital scalps of postpubertal macaques were also cultured and used as a control. The dermal papilla cells obtained from three different male and female macaques were used for each study.



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  		Figure 1. Phase contrast photomicrographs of isolated dermal papillae. a, bald frontal dermal papilla from the postpubertal macaque; b, occipital dermal papilla from the postpubertal macaque; c, prebald frontal dermal papilla from the prepubertal macaque; d, occipital dermal papilla from the prepubertal macaque. Magnification, x180; scale bar, 50 µm.

 
For culturing outer root sheath cells, anagen hair follicles were dissected from the occipital skin of three different male and female macaques in the postpubertal stage and treated with 0.2% collagenase (Sigma) in DMEM for 30 min at 37 C to remove the connective tissue sheath. After rinsing with PBS without calcium and magnesium, the hair follicles were transferred into dishes and cultured with DMEM supplemented with 10% FBS, epidermal growth factor (10 ng/ml, Sigma), insulin (5 µg/ml, Sigma), and hydrocortisone (0.5 µg/ml, Sigma). On the fourth day, the medium was changed to keratinocyte growth medium (KGM) (Clonetics, San Diego, CA) containing epidermal growth factor (10 ng/ml), insulin (5 µg/ml), hydrocortisone (0.5 µg/ml), and bovine pituitary extracts (30 µg protein/ml). The concentration of calcium in the medium was adjusted to 0.06 mM. After 2 weeks, the cells were dispersed with 0.02% EDTA and 0.1% trypsin treatment and subcultured. The cells were incubated at 37 C in a humidified atmosphere of air containing 5% CO2. Second and third passage cells were used in this study. For kinetic studies of dermal papilla cells, the cells were counted on days 1, 2, 3, 4, 5, and 7, using a hemocytometer chamber.

Coculture of dermal papilla cells and outer root sheath cells
Dermal papilla cells were inoculated at a density of 1 x 104 cells/well into type I collagen-coated multiplates (24 wells) (Corning, New York, NY) and cultured with DMEM supplemented with 10% charcoal-treated FBS. After a 24-h incubation, the medium was discarded and outer root sheath cells (1.5 x 104 cells/well) were added with KGM without bovine pituitary extracts. Further, bald frontal dermal papilla cells from postpubertal macaques and outer root sheath cells were cocultured using transwells (Becton Dickinson, Bedford, MA) to determine which type of cell proliferation was stimulated by coculture or inhibited by testosterone. Some outer root sheath cells were cultured on the membrane of transwells coated with type I collagen and those were placed in the wells in which dermal papilla cells had been cultured on the bottom.

Effects of testosterone and an antiandrogen
Testosterone (Sigma) was dissolved in ethanol and diluted with DMEM or KGM at 10-7 to 10-10 M. A potent androgen receptor blocker, RU 58841 (17), was dissolved in ethanol and diluted with KGM at 10-10 M. One day after attachment of dermal papilla cells to a dish, testosterone with or without RU 58841 was added to each culture. Cells were refed 3 days later and counted using a hemocytometer chamber, 7 days after cultivation of dermal papilla cells.

Effect of topical RU 58841 on hair regrowth
Nine stumptailed macaques (5–15 yr old, seven male and two female) were divided into three groups (three animals in a 5% RU 58841 group, three animals in a 0.5% RU 58841 group and three animals in a vehicle group). RU 58841 was dissolved in a vehicle solution consisting of 50% propylene glycol, 30% isopropanol, 2% isopropyl myristate, and 18% distilled water. Each animal in the above three groups received 0.5 ml topical applications of solutions in an approximately 50-cm2 area of the frontal bald scalp once per day, 5 days per week for 18 months.

The effects of RU 58841 on hair regrowth as well as follicular enlargement were evaluated by monthly photographic recordings of the frontal scalp and micromorphometric analysis of follicular size and cyclic changes in biopsied scalp skin. Four-millilmeter punch biopsies of the frontal scalp were performed at 0, 6, and 11 months during the whole experimental period. Serial paraffin sections were cut from the specimens. After staining with hematoxylin and eosin, all hair follicles in each section were traced under a projecting microscope. Using a computer-assisted image program, the follicular length, from the epidermal surface to follicular base, was measured and each hair follicle was defined according to their cyclic phases;telogen (resting), early anagen, late anagen (growing), and catagen (involuting). The histograms representing the proportional population and follicular size of each cyclic phase were made for analysis of the sequential changes of follicular transformation from the pre- to posttreatment stages, according to a previously reported method (12, 13, 15). A conversion rate from short vellus to long terminal follicles was calculated from the histograms of 6- and 11-month treatments compared with that of the pretreatment stage.

Statistics
Results are presented as means ± SEM. All experiments were analyzed using Student’s t test for paired samples. Differences of P < 0.05 were regarded as significant.


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
The mean length from the dome to the base of prebald frontal dermal papilla (81.2 ± 3.7 µm, n = 12) was almost the same as that of the occipital dermal papilla (84.0 ± 4.4 µm, n = 12) from three different macaques in the prepubertal stage whereas the length of bald frontal dermal papilla (75.0 ± 5.2 µm, n = 12) was shorter than that of the occipital dermal papilla (153.1 ± 4.8 µm, n = 12) from six different macaques in the postpubertal stage.

Bald and prebald frontal dermal papilla cells became nearly confluent within 10 days after inoculation at a density of 4 x 104 cells/35-mm dish. The growth curves of each type of cells are shown in Fig. 2Go. Cell numbers at days 5 and 7 were significantly greater in prebald frontal dermal papilla cells from prepubertal macaques and occipital dermal papilla cells from postpubertal macaques than in bald frontal dermal papilla cells from postpubertal macaques. During the log phase, the mean population doubling time (69.02 ± 5.92 h) of bald frontal dermal papilla cells from postpubertal macaques was significantly (P < 0.01) longer than those of prebald frontal dermal papilla cells from prepubertal macaques (37.0 ± 1.63 h) and occipital dermal papilla cells from postpubertal macaques (39.49 ± 4.13 h).



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  		Figure 2. Growth curves of the cultured bald frontal, prebald frontal, and occipital dermal papilla cells. Dermal papilla cells (4 x 104 cells/dish) were plated in 35-mm dishes. Each point on the curve represents the mean ± SEM (n = 6). {circ}, Bald frontal dermal papilla cells (bFDPC) from the postpubertal macaque; {triangleup}, prebald frontal dermal papilla cells from the prepubertal macaque; {square}, occipital dermal papilla cells from the postpubertal macaque. Asterisks denote cell numbers significantly different (*, P < 0.05; **, P < 0.01; ***, P < 0.001) from those of bFDPC.

 
Testosterone (10-7 to 10-10 M) showed no effects on proliferation of any types of dermal papilla cells cultured alone (data not shown). No morphological changes of the cells treated with testosterone were observed under a light microscope. The inhibitory effects were shown only when bald frontal dermal papilla cells from postpubertal macaques and outer root sheath cells were cocultured in the same wells of multiplates (Table 1Go). The total number of outer root sheath cells cocultured with either type of dermal papilla cells increased by more than the sum of the number of dermal papilla cells and outer root sheath cells cultured alone. Testosterone (10-10 M) significantly decreased the total number of bald frontal dermal papilla cells and outer root sheath cells in coculture. RU 58841 antagonized this testosterone-elicited inhibition. By contrast, the total cell numbers in cocultures of prebald frontal or occipital dermal papilla cells and outer root sheath cells were not affected by testosterone. Testosterone (10-10 M) had no effect on proliferation of outer root sheath cells cultured alone.


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  		Table 1. Effects of testosterone on proliferation of dermal papilla cells and outer root sheath cells cultured alone and together

 
Table 2Go shows that the number of outer root sheath cells was increased by coculture with dermal papilla cells compared with that of outer root sheath cells cultured alone (see Table 1Go). Testosterone (10-10 M) inhibited this stimulation. By contrast, the number of dermal papilla cells was not affected by coculture or testosterone.


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  		Table 2. Inhibitory effect of testosterone on proliferation of outer root sheath cells cocultured with bald frontal dermal papilla cells

 
In the photographic views of the frontal bald scalp, all three animals treated with 5% RU 58841 showed a dramatic effect of hair regrowth as early as 2 months after treatment. All animals showed a remarkable increase of hair density and length at 4 months after treatment with 5% RU 58841 compared with the pretreatment time (Fig. 3Go, a and b). The progressive effects of hair regrowth, namely increased length and thickening of the caliber of individual hairs, were continuously observed for 6–7 months in three animals. Thereafter, these regrown terminal hairs were maintained throughout the period of treatment. The effect of 0.5% RU 58841 on hair regrowth (Fig. 3Go, c and d) was much weaker than that of 5%. The hair density increased a slight degree in all three animals and a maintenance of the hairiness was observed throughout the treatment period. The vehicle-treated group showed no signs of hair regrowth during the entire treatment period (Fig. 3Go, e and f), though occasional mild thickening of hairs was observed in one animal.



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  		Figure 3. Photographs showing effects of topical RU 58841 on hair regrowth in the bald frontal scalps of the stumptailed macaques. Increased density and length of hairs were observed in a scalp at 4 months after treatment with 5% RU 58841 (b) compared with the scalp at the pretreatment time (a). A slight increased density of hairs was noticed in a scalp at 4 months after treatment with 0.5% RU 58841 (d) compared with the scalp at the pretreatment time (c). A vehicle-treated scalp showed no signs of hair regrowth (e, at the pretreatment time and f, at 4 months).

 
Further micromorphometric analysis showed that 5% RU 58841 enhanced not only a conversion rate from vellus to terminal follicles but also a population of anagen hair follicles. The 5% RU 58841 group had a 67% increase at 6 months and a 33% increase at 11 months after treatment in an average conversion rate. A 0.5% RU 58841 group showed an 80% decrease at 6 months and a 36% decrease at 11 months after treatment in an average conversion rate. A vehicle group exhibited a 15% decrease at 6 months and a 20% decrease at 11 months in an average conversion rate.

Finally, our physiological and laboratory examinations showed there were no significant abnormal values in the measurements of body weight, serum levels of testosterone, dihydrotestosterone, and LH, and hematological and blood chemistry examinations in all animals in all experimental groups.


   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
Androgens are potent regulators of human hair growth in males and females. Hair follicles distributed in specific regions of the body appear to have an inherited susceptibility for androgen-dependent growth. Androgen receptors (AR) have been immunocytochemically (18, 19) and biochemically (20) detected in the hair follicles of human skin. Furthermore, the method for culturing hair follicles including the outer root sheath cells and dermal papilla cells has been established (16, 21, 22). Specific AR have been detected in dermal papilla cells; levels are higher in cells from beard follicles than in cells from normal scalps (5, 6). Cultured dermal papilla cells derived from beard hair follicles have the ability to induce a testosterone-dependent proliferation of cocultured outer root sheath cells (4). In men with a trait for baldness, postpubertal elevation of testosterone causes irreversible regression of the scalp hair follicles (10). A similar epigenetic phenomenon has been observed in the frontal scalps of adult stumptailed macaques (14). In our in vivo studies of the macaques, finasteride (a type II 5{alpha}-reductase inhibitor) (15) and RU 58841 (an androgen receptor blocker), stimulated hair growth (Fig. 3Go). Our micromorphometric analysis also showed that a sufficient dose (5%) of RU 58841 caused vellus hair follicles to regrow into terminal hair follicles and increased the population from telogen to anagen hair follicles, indicating a result of increased density and length of hairs from the photographic views. These studies indicate that stumptailed macaques are a pertinent model for human androgenetic alopecia.

Our data suggest that bald frontal dermal papilla cells play an important role in inhibitory actions of testosterone on proliferation of outer root sheath cells. Table 1Go, however, also indicates that bald frontal dermal papilla cells cocultured without testosterone can stimulate proliferation of outer root sheath cells. One potential explanation is that this may be due to the secretion of some soluble mitogenic substances from dermal papilla cells. The involvement of these soluble substances produced by dermal papilla cells derived from hair follicles in other body sites has been demonstrated in in vitro studies (23, 24, 25).

Although the soluble mitogenic substances remain unknown, several possible mechanisms might explain this apparent testosterone-dependent inhibition. Testosterone can bind to AR after diffusing through the plasma membrane; it can also be metabolized intracellularly by 5{alpha}-reductase to 5{alpha}-dihydrotestosterone, which can also bind and activate the AR (26). One possibility is that the androgen-AR complexes may directly repress the production and/or secretion of soluble mitogenic substances. Another possibility is that new inhibitory substances may be induced by androgen-AR complexes in bald frontal dermal papilla cells which may then inhibit proliferation of epithelial cells of hair follicles. Yet another possibility is that androgen may induce growth factor(s) in dermal papilla cells that can then trigger an induction of some inhibition of epithelial cell proliferation. Either way, the androgen-induced repressor(s) or androgen-repressed growth factors in dermal papilla cells appear to play an essential role in hair growth/baldness.

Interestingly, dermal papilla cells derived from the prebald frontal scalps of juvenile monkeys exhibited no testosterone-induced inhibitory actions on outer root sheath cell proliferation. Our data, therefore, support the hypothesis that the development of baldness in stumptailed macaques is an age-dependent phenomenon (11). Most male and female animals begin to show early signs of baldness after age 4, which corresponds with sexual maturity (11) and the postpubertal elevation of serum testosterone (14). Together, the present study suggests that the role of dermal papilla cells in the inhibitory action of testosterone on the epithelial cells can be linked to hereditary factors, and the elevation of serum testosterone to adult levels after age 4 may be able to initiate and promote genetic programming of the frontal dermal papilla cells. This study is comparable with the earlier study indicating that castration before or after puberty prevents the induction or further development of baldness in the absence of exogenous testosterone and suggesting that continued exposure to androgens may be required in hair follicles to cause an alteration in gene expression (10).

Our study also revealed differences in biological characteristics between prebald and bald dermal papilla cells, even when those cells were cultured alone. First, the doubling time of bald frontal dermal papilla cells was longer than that of prebald frontal dermal papilla cells. Second, bald frontal dermal papilla cells subcultured more than five times no longer proliferated, but prebald frontal dermal papilla cells could be subcultured at least seven times (data not shown). These two characteristics might be the results of genetic factors as well as of testosterone. The mean size of bald frontal dermal papillae is approximately half that of occipital dermal papillae from the postpubertal macaques, although the mean size of prebald dermal papillae is the same as that of occipital dermal papillae from prepubertal macaques. Androgens may gradually decrease the size of frontal dermal papillae after puberty. The dermal papilla from the beard-hair follicle is reported to be much larger than that from the scalp-hair follicle, suggesting that androgens increase the dermal papilla size (5). The difference in size of occipital dermal papillae between prepubertal and postpubertal macaques seems to result from growth of the animal bodies themselves according to their age.

This in vitro study also reconfirms that the frontal hair follicle of stumptailed macaques is an androgen-dependent organ, showing direct effects of testosterone on epithelial cells cocultured with bald frontal dermal papilla cells. Other androgen-regulated factors may be isolated in further studies. To the best of our knowledge, this is the first paper demonstrating the inhibitory effect of testosterone on the proliferation of outer root sheath cells cocultured with dermal papilla cells derived from the bald frontal scalp.


   Acknowledgments
 
The authors wish to thank Dr. Lynn Allen-Hoffmann for critically reading the manuscript. We thank Carol Thieme and Sacha Ramirez for their technical assistance and Mary Schatz for secretarial work.


   Footnotes
 
1 This work was partly supported by NIH Grants RR-00167 and CA-68568 as well as Roussel Uclaf Company. Part of these results were presented in preliminary forms at the proceedings of the First Tricontinental Meeting of Hair Research Societies, Brussels Belgium, 8–10 October, 1995 (Uno H, Obana N, Cappas A, Bonfils A, Battmann T, Philibert D). This is Publication No. 36-040 of the WRPRC. Back

Received July 10, 1996.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Oliver RF 1969 Regeneration of the dermal papilla and its influence on whisker growth. In: Montagna W, Dobson RL (eds) Advances in Biology of Skin. Pergamon Press, Oxford, vol 9:19–33
  2. Jahoda CAB, Horne KA, Oliver RF 1984 Induction of hair growth by implantation of cultured dermal papilla cells. Nature 311:560–562[CrossRef][Medline]
  3. Yuspa SH, Wang Q, Weinberg WC, Goodman L, Ledbetter S, Dooley T, Lichti U 1993 Regulation of hair follicle development: an in vitro model for hair follicle invasion of dermis and associated connective tissue remodeling. J Invest Dermatol [Suppl] 101:27S–32S[CrossRef]
  4. Itami S, Kurata S, Sonoda T, Takayasu S 1991 Mechanism of action of androgen in dermal papilla cells. Ann NY Acad Sci 642:385–395[Medline]
  5. Randall VA, Thornton MJ, Hamada K, Redfern CPF, Nutbrown M, Ebling FJG, Messenger AG 1991 Androgens and the hair follicle cultured human dermal papilla cells as a model system. Ann NY Acad Sci 642:355–375[Medline]
  6. Randall VA, Thornton MJ, Hamada K, Messenger AG 1992 Mechanism of androgen action in cultured dermal papilla cells derived from human hair follicles with varying responses to androgens in vivo. J Invest Dermatol [Suppl] 98:86S–91S[CrossRef]
  7. Itami S, Kurata S, Takayasu S 1990 5{alpha}-Reductase activity in cultured human dermal papilla cells from beard compared with reticular dermal fibroblasts. J Invest Dermatol 94:150–152[CrossRef][Medline]
  8. Imperato-McGinley J, Guerrero L, Gautier T, Peterson RE 1974 Steroid 5{alpha}-reductase deficiency in man: an inherited form of male pseudohermaphroditism. Science 186:1213–1215[Abstract/Free Full Text]
  9. Ebling FJG 1986 Hair follicles and associated glands are androgen targets. J Clin Endocrinol Metab 15:319–339
  10. Hamilton JB 1942 Male hormone stimulation is a prerequisite and an incitant in common baldness. Am J Anat 71:451–480[CrossRef]
  11. Goldfoot DA, Slob AK, Scheffler G, Robinson JA, Wiegand SJ, Cords J 1975 Multiple ejaculations during prolonged sexual tests and lack of resultant serum testosterone increases in male stumptailed macaques (M. arctoides). Arch Sex Behavior 4:547–560
  12. Rittmaster RS, Uno H, Povar ML, Mellin TN, Loriaux DL 1987 The effects of N,N-diethyl-4-methyl-3-oxo-4-aza-5{alpha}-androstane-17ß-carboxamide, a 5{alpha}-reductase inhibitor and antiandrogen, on the development of baldness in the stumptailed macaque. J Clin Endocrinol Metab 65:188–193[Abstract]
  13. Uno H 1987 Stumptailed macaques as a model of male-pattern baldness. In: Maibach HI, Lowe NJ (eds) Models in Dermatology. S Karger AG, Basel, pp 159–169
  14. Uno H, Alsum PB, Bauers K, de Waal FBM 1991 Serum androgens in stumptailed macaques (Macaca arctoides). In: Ehara A (ed) Primatology Today. Elsevier Science Publishers, Amsterdam, pp 419–420
  15. Rhodes L, Harper J, Uno H, Gaito G, Audette-Arruda J, Kurata S, Berman C, Primka R, Pikounis B 1994 The effects of finasteride (Proscar) on hair growth, hair cycle stage, and serum testosterone and dihydrotestosterone in adult male and female stumptail macaques (Macaca arctoides). J Clin Endocrinol Metab 79:991–996[Abstract]
  16. Williams D, Profeta K, Stenn KS 1994 Isolation and culture of follicular papillae from murine vibrissae: an introductory approach. Br J Dermatol 130:290–297[CrossRef][Medline]
  17. Battmann T, Bonfils A, Branche C, Humbert J, Goubet F, Teutsch G, Philibert D 1994 RU 58841, a new specific topical antiandrogen: a candidate of choice for the treatment of acne, androgenetic alopecia and hirsutism. J Steroid Biochem Molec Biol 48:55–60[CrossRef][Medline]
  18. Choudry R, Hodgins MB, Van der Kwast TH, Brinkmann AO, Boersma WJA 1992 Localization of androgen receptors in human skin by immunohistochemistry: implications for the hormonal regulation of hair growth, sebaceous glands and sweat glands. J Endocrinol 133:467–475[Abstract]
  19. Liang T, Hoyer S, Yu R, Soltani K, Lorincz AL, Hiipakka RA, Liao S 1993 Immunocytochemical localization of androgen receptors in human skin using monoclonal antibodies against the androgen receptor. J Invest Dermatol 100:663–666[CrossRef][Medline]
  20. Sawaya ME 1992 Purification of androgen receptors in human sebocytes and hair. J Invest Dermatol [Suppl] 98:92S–96S[CrossRef]
  21. Limat A, Noser FK 1986 Serial cultivation of single keratinocytes from the outer root sheath of human scalp hair follicles. J Invest Dermatol 87:485–488[CrossRef][Medline]
  22. Messenger AG, Senior HJ, Bleehen SS 1986 The in vitro properties of dermal papilla cell lines established from human hair follicles. Br J Dermatol 114:425–430[CrossRef][Medline]
  23. Reynolds AJ, Jahoda CAB 1991 Hair follicle stem cells? A distinct germinative epidermal cell population is activated in vitro by the presence of hair dermal cells. J Cell Sci 99:373–385[Abstract/Free Full Text]
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  26. Rommerts FFG 1990 Testosterone: an overview of biosynthesis, transport, metabolism, and action. In: Nieschlag E, Behre HM (eds) Testosterone Action Deficiency Substitution. Springer-Verlag, Berlin, pp 1–22



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Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals