Title: Inhibition of hair growth by testosterone in the presence of dermal papilla cells from the frontal bald scalp of the postpubertal stumptailed macaque.

Title Abreviation: Endocrinology
Date of Pub: 1997 Jan
Author: Obana N; Chang C; Uno H;
Issue/Part/Supplement: 1
Issue: 138
Pagination: 356-61
MESH Headings: Alopecia*; Animal; Cell Division*; Cells, Cultured*;
Female; Hair*; Imidazoles*; Macaca*; Male; Nitriles*; Skin*; Support,
Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Testosterone*; -PG-;
Journal Title Code: EGZ
Publication Type: JOURNAL
Date of Entry: 970123N
Entry Month: 9703
Index Priority: 1
Language: Eng
Unique Identifier: 97131967
Unique Identifier: 97131967
ISSN: 0013-7227


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 millimeter punch biopsies of 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 post-treatment stages, according to a previously reported method. 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 pre-treatment stage. Snip… 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 pre-treatment time. 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 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, though occasional mild thickening of hairs was observed in one animal. 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 converison 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 experimental groups.

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.

Abstract By: Author
Address: Regional Primate Research Center, University of Wisconsin,
Madison 53715-1299, USA.

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