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- Publisher
- Karger
- Copyright
- © 1994 S. Karger AG, Basel
- ISSN
- 1660-5527
- eISSN
- 1660-5535
- DOI
- 10.1159/000211265
- Publisher site
- See Article on Publisher Site
Abstract
Skin Pharmacol 1994;7:5-7 M arty E. Saw aya Biochemical Mechanisms Regulating Human Hair Growth A b s tra c t K ey W ords The human hair follicle cycles in active growth and resting Androgens phases controlled by a complex network of biochemical pro 5a-Reductase cesses, yet to be fully understood. It is well known that hair Aromatase enzyme follicles on scalp respond to androgens by a shortening of the Human hair growth anagen growth phase causing hairs to regress to a finer, thinner Androgenetic alopecia texture. The target tissue androgens, testosterone, and dihy drotestosterone can circulate systemically to skin or can be formed locally in hair follicles and sebaceous glands by spe cific enzymes in the steroid cascade. Kinetic constants have been evaluated for several enzymes which mediate dihydrotes tosterone formation, including 5a-reductase, and the cyto chrome P-450 aromatase enzyme in isolated human hair folli cles and sebaceous glands from scalp of men and women with androgenetic alopecia. The levels o f these enzymes differed between men and women, and from frontal versus occipital sites within the same patient, indicating that similar steroid mechanisms may be taking place in men and women, but the amount or level of enzymes vary, perhaps explaining why men have more severe patterns of hair loss than women. Knowing the differences between men and women with androgenetic alopecia could shape more effective treatment options in the future. gress and recede in genetically susceptible Androgens have been known to stimulate men and women. terminal hair growth in certain body regions; Our studies have focused on many o f the however in scalp, adrogens have an effect of androgen-mediated biochemical mechanisms shortening the anagen growth phase of the influencing hair growth as it relates to andro- hair cycle, causing hair follicles (HF) to re M artyE. Sawaya, MD, PhD @1994 University of Florida S. Karger AG. Basel Division o f Dermatology 1011-0283/94/ PO Box 100277 0072-000552.75/0 Gainesville, FL 32610-0277 (U SA ) Table 1. Aromatase and 5a-R levels in human HF uterus, breast and even brain [2-4]. Aroma tase has been recognized in mediating tumor- Aromatase 5a-R associated processes some of these tissues, and is regulated by cellular factors, such as Women occipital 52 ± 5 32 ± 8 cAMP, growth factors, gonadotropins, and 30 ± 4 frontal 56 ± 4 even the substrates that utilize it [5, 6]. 20± 3 78 + 8 Men occipital To assess these two very important en frontal 8 ± 3 164 ± 7 zymes, scalp biopsy specimens from frontal Values stated are the mean ± SE of Vmax values and occipital sections were obtained from (pmol/min/mg protein) obtained from microsomal each patient (10 men and 10 women, from 18 fraction of isolated human HF from the occipital and to 35 years of age). Results from the analysis frontal scalp sections of 10 men and 10 women with [7] of Aromatase revealed that the frontal HFs AGA. in both men and women had less aromatase than in the occipital HFs. Overall, HF from women had approximately 3-5 times the level of aromatase in frontal and occipital HFs in comparison to men (table 1). In women, where the frontal hairline is usually spared, genetic alopecia (AGA). Many questions of the frontal HFs had higher levels of aromatase ten asked about men and women who suffer with AGA are the following. (1) Are the bio than receded, regressed HFs from neighbor chemical mechanisms taking place in hair ing sites. Men with AGA had minimal levels follicles of men with AGA the same as in of aromatase enzyme in their frontal HFs. Conclusions drawn from the study in women? (2) Why do men usually have a cluded: (1) females with AGA had nearly 2- more severe pattern of hair loss than women? fold 5a-R in frontal HF versus occipital HFs, (3) Are the HF in the front of the scalp the and yet nearly one third the amount of en same as those in the occipital or vertex re gion of the scalp, rendering the same sensi zyme as men with AGA and (2) men with tivity to androgens? (4) Are there always sys AGA have greater 5a-R in their frontal HFs, with minimal levels of Aromatase. In women, temic elevated androgen levels in women we may conclude that a sparing of the frontal with AGA? hairline may be due to higher levels of aroma To answer some o f these questions, studies were done to assess the levels of androgen tase, limiting the formation of 5a-reduced converting enzymes, such as 5a-reductase (5a- substrates that can bind to the androgen re R), and the cytochrome P-450 aromatase en ceptor to initiate androgen-mediated cellular zyme (Aromatase) in H F of men and women events. The higher levels of 5a-R and low aro with AGA. matase levels seen in men with AGA may be The 5a-R enzyme mediates conversion of due to formation of 5a-reduced products de creasing the levels of available substrate for testosterone to dihydrotestosterone, and it is the aromatase enzyme to utilize. thought that there may be two forms of 5a-R, In conclusion, similar hormone enzyme one being specific in whole skin, versus pros mechanisms may be working in men and tate [1], The aromatase enzyme has been shown to women with AGA; however, the levels or be widely distributed in adipose tissue, and amounts of enzymes and cellular factors may differ between men and women with AGA, reproductive tissues, such as ovary, placenta, 6 Sawaya Androgens Regulating H air Growth perhaps giving some explanation of the severe Knowing the biochemical mechanisms in patterns of hair loss noted in men with AGA, men and women with AGA may shape our versus their female counterparts, who display treatment options in the future, where formu a more diffuse, centralized, thinning pattern lations for men may be different from those of hair loss. for women with AGA. R eferences 1 Itami S, K urata S, Sonoda T, Ta 3 Balthazart J, Foidart A, Harada N: 6 Bcrkovitz GC, Fujimoto M, Brown kayasu S: Characterization o f 5a- Immunocytochemical localization T R , Brodie AM, Migeon CJ: Aro- reductase in cultured hum an dermal o f aromatase in the brain. Brain Res matase activity in cultured hum an papilla cells from beard and occipi 1990;514:327-333. genital skin fibroblasts. J Clin Endo tal scalp hair. J Invest Dermatol 4 Ryan KJ: Biochemistry o f aroma crinol Metab 1984;59:665-671. 1991;96:56-60. tase: Significance to female repro 7 Sawaya ME: Steroid chemistry and 2 Evans CT, Corbin CJ, Saunders CT, ductive physiology. Cancer Res hormone controls during the hair Merrill JC, Simpson ER, Mendelson 1982;42(suppl):3342-3344. follicle cycle. Ann NY Acad Sci CR. Regulation o f estrogen biosyn 5 Zimniski SJ, Brandt ME, Covey DF, 1991;642:376-385. thesis in hum an adipose stromal Puett D: Inhibition o f aromatase ac cells. J Biol Chem 1987:262:6914— tivity and endocrine responsive tu 6920. m or growth by 10-propargylestr-4- ene-3,17-dione, and its proprionate derivative. Steroids 1987;50:135—
Journal
Skin Pharmacology and Physiology – Karger
Published: Jan 1, 1994
Keywords: Aromatase enzyme; Human hair growth; Androgenetic alopecia; Androgens; 5a-Reductase