Journal of Investigative Dermatology (1984) 82, 62–66; doi:10.1111/1523-1747.ep12259135
Androgen Metabolism by Isolated Hairs from Women with Idiopathic Hirsutism Is Usually Normal
Sally P Glickman and Robert L Rosenfield
Departments of Medicine and Pediatrics, Pritzker School of Medicine, The University of Chicago, Chicago, Illinois, U.S.A.
Received 13 May 1983; Accepted 27 July 1983.
Top of pageAbstract
We have tested the hypothesis that idiopathic hirsutism (IH) may be due to abnormality of androgen-responsive hair follicles. Because androgen metabolism within target cells is an important determinant of androgen action, we have analyzed the rates of formation and disposition of the major mediators of androgen action, testosterone (T) and dihydrotestosterone (DHT).
In normal women, the pattern of androgen metabolism by growing hairs favors T predominance over DHT and inactivation of both these 17
-hydroxysteroids to 17-ketosteroids. This pattern results greatly from predominance of 17
-hydroxysteroid dehydrogenation. For example, in normal women's scalp hair, DHT disposition to 5
-androstanedione proceeded at the rate of 8.6
2.0 (SEM) %/
g DNA/min, whereas DHT was formed from T at a rate of 0.14
0.02, and T was formed from androstenedione at a rate of 0.60
0.12, all significantly different from one another. Both the formation of 17-ketosteroids and the apparent 5
-reductase activity were exaggerated in the pubic hair of men; whether these differences are site-, sex-, or androgen-related, remains to be determined. Pubic hairs tended to metabolize androgens at a greater rate than did scalp hair. This was related to the significantly greater DNA content of plucked pubic hairs, a difference unrelated to sex or androgen levels.
Women with IH had heterogeneous pubic hair abnormalities. Only 1 of the 4 IH patients studied had abnormal pubic hair follicle androgen metabolism, with the greatest abnormality being an exaggerated rate of 17
-hydroxysteroid inactivation to 17-ketosteroids. Two of the other 3 IH cases had increased DNA content of plucked pubic hairs, a different kind of exaggeration of normal, which suggests an abnormality of hair follicle growth unrelated to androgen sensitivity. We favor the concept that abnormalities which reflect fundamental defects in the regulation of hair growth.
Top of pageReferences
- Hatch, R, Rosenfield, RL, Kim, MH, Tredway, D: Hirsutism: implications, etiology, and management. Am J Obstet Gynecol 1981 140: 815–830, | PubMed | ChemPort |
- Maroulis, GB: Evaluation of hirsutism and hyperandrogenemia. Fertil Steril 1981 36: 273–305, | PubMed | ChemPort |
- Takayasu, S: Metabolism and action of androgens in skin. Int J Dermatol 1979 18: 681–692, | PubMed | ChemPort |
- Attramadal, A, Weddington, S, Naess, O, Djoseland, O, Hansson, V: Androgen receptors in male sex tissues of rats and humans. Prostatic Disease 1976 Edited by AR Liss, New York, pp 189–203,
- Nimrod, A, Rosenfield, RL, Otto, P: Relationship of androgen action to androgen metabolism in isolated rat granulosa cells. J Steroid Biochem 1980 13: 1015–1019, | Article | PubMed | ChemPort |
- Kuttenn, F, Mowszowicz, I, Schaison, G, Mauvais-Jarvis, P: Androgen production and skin metabolism in hirsutism. J Endocrinol 1977 75: 83–91, | PubMed | ChemPort |
- Fazekas, AG, Lanthier, A: Metabolism of androgens by isolated human beard hair follicles. Steroids 1971 18: 367–379, | Article | PubMed | ChemPort |
- Miyazaki, M, Takayasu, S, Karakawa, T, Aono, T, Kurachi, K, Matsumoto, K: Activity of testosterone 5
-reductase in the hair follicles of women with polycystic ovaries. J Endocrinol 1978 78: 445–446, | PubMed | ChemPort | - Schweikert, HJ, Wilson, JD: Regulation of human hair growth by steroid hormones. I. Testosterone metabolism in isolated hairs. J Clin Endocrinol Metab 1974 38: 811–819, | PubMed | ChemPort |
- Schweikert, HJ, Wilson, JD: Regulation of human hair growth by steroid hormones. II. Androstenedione metabolism in isolated hairs. J Clin Endocrinol Metab 1974 39: 1012–1019, | PubMed | ChemPort |
- Glickman, SP, Rosenfield, RL, Bergenstal, RM, Helke, J: Multiple androgenic abnormalities, including elevated free testosterone, in hyperprolactinemic women. J Clin Endocrinol Metab 1982 55: 251–257, | PubMed | ChemPort |
- Moll, GW Jr, Rosenfield, RL: Testosterone binding and free plasma androgen concentrations under physiological conditions: characterization by flow dialysis technique. J Clin Endocrinol Metab 1979 49: 730–736, | PubMed | ChemPort |
- Van Scott, EJ, Reinertson, RP, Steinmuller, R: The growing hair roots of the human scalp and morphologic changes therein following amethopterin therapy. J Invest Dermatol 1957 29: 197–204, | PubMed | ChemPort |
- Becker, H, Grabasch, E, Hoffmann, C, Voight, KD: Metabolism and mode of action of androgens in target tissues of male rats. Acta Endocrinol (Copenh) 1973 73: 407–416, | PubMed | ChemPort |
- Sansone-Bazzano, G, Reisner, RM, Bazzano, G: Conversion of testosterone-1,2,H3 to androstenedione-H3 in the isolated hair follicle of man. J Clin Endocrinol Metab 1972 34: 512–515, | PubMed | ChemPort |
- Hay, JB, Hodgins, MB: Distribution of androgen metabolism enzymes in isolated tissues of human forehead and axillary skin. J Endocrinol 1978 79: 29–39, | PubMed | ISI | ChemPort |
- Itami, S, Takayasu, S: Activity of 3
-hydroxysteroid dehydrogenase
4-5isomerase in the human skin. Arch Dermatol Res 1982 274: 289–294, | Article | PubMed | ISI | ChemPort | - Wilson, J: Dihydrotestosterone formation in cultured human fibroblasts. J Biol Chem 1975 250: 3498–3504, | PubMed | ChemPort |
- Flamigni, C, Collins, WP, Koullapis, EN, Craft, I, Dewhurst, C, Sommerville, J: Androgen metabolism in human skin. J Clin Endocrinol Metab 1971 32: 737–743, | PubMed | ISI | ChemPort |
- Kuttenn, F, Jarvis, P: Testosterone 5
-reduction in the skin of normal subjects and of patients with abnormal sex development. Acta Endocrinol (Copenh) 1975 79: 164–176, | PubMed | ChemPort | - Mauvais-Jarvis, P: Simultaneous determination of urinary androstanediol and testosterone as an evaluation of human androgenicity. J Clin Endocrinol Metab 1973 36: 452–459, | PubMed | ChemPort |
- Horton, R, Hawks, D, Lobo, R: 3
,17
-Androstanediol glucuronide in plasma. J Clin Invest 1982 69: 1203–1206, | PubMed | ChemPort |