Testosterone Metabolism in Skin
It appears warranted to draw several tentative conclusions from these studies. First, the reduction of testosterone to dihydrotestosterone by slices of various types of human skin appears to correlate with the capacity for the skin to grow under the influence of androgens, skin from the perineal areas exhibiting the highest rates observed. Second, as the result of studies on dihydrotestosterone formation in skin biopsies from patients with the syndrome of testicular feminization and on the relation between age and the capacity of human prepuce to perform this conversion, it is possible that the ability to reduce testosterone to dihydrotestosterone may be a limiting factor in the androgen-mediated growth of these tissues. Third, the appearance of the enzyme which performs this conversion in the anlage of the perineal skin early in embryonic development appears to fulfill the requirements of an initial androgen receptor, suggesting the possibility that this reaction may be critical to the male differentiation of the genital skin. Fourth, the factors which regulate the level of the enzyme for dihydrotestosterone formation have not yet been identified. Finally, preliminary evidence suggests that dihydrotestosterone formation may also be involved in the androgen-mediated growth of sebaceous glands and hair.
This working hypothesis, namely that dihydrotestosterone may be involved critically in the androgen-stimulated growth and differentiation of human skin as well as in the accessory organs of reproduction, leaves a number of questions concerning androgen action unanswered. It does not provide an explanation for testosterone-enhanced growth of muscle or for testosterone action in tissues which lose the ability to form dihydrotestosterone with age (6, 11). The hypothesis does have considerable potential explanatory value, however, for the elucidation of testosterone action in skin and in other tissues both in normal state and in a variety of pathological conditions.
Unable to display preview. Download preview PDF.
- 2.Farnsworth, W.E., Brown, J.R.: J. Amer. med. Ass. 183, 436 (1963).Google Scholar
- 10.Wilson, J.D., Loeb, P.M.: In: Developmental and Metabolic Control Mechanisms and Neoplasia (M. D. Anderson Hospital and Tumor Institute), Baltimore®: Williams and Wilkins Co., 1965, p. 375.Google Scholar
- 14.Dorfman, R.I., Shipley, R.A.: Androgens, Biochemistry, Physiology and Clinical Significance, New York: Wiley and Sons, 1956, p. 118.Google Scholar
- 15.Saunders, F.J.: Nat. Cancer Inst. Monogr. 12, 139 (1963).Google Scholar
- 16.Hilgar, A.G., Hummel, D.J.: In E.P. Vollmer (Editor), Androgenic and Myogenic Endocrine Bioassay Data, Part 11, National Cancer Institute, Bethesda, 1964, p. 15.Google Scholar
- 17.Gomez, E.C., Hsia, S.L.: Biochemistry 7, (1968).Google Scholar
- 19.Turner, H.H.: The Clinical Use of Testosterone, W.O. Thompson (Editor), Springfield: Thomas, 1950.Google Scholar
- 20.Heinrichs, W.L., Karsznia, R., Wyss, R., Hermann, W.L.: Clin. Res. 17, 143 (1969).Google Scholar
- 23.Federman, D.D.: Abnormal Sexual Development, Philadelphia, Saunders, 1967Google Scholar
- 24.Wieland, R.G., Chen, J.C., Chambers, D.: Clin. Res. H., 18, 605 (1970).Google Scholar
- 26.McGuire, J.S., Jr., Tomkins, G.M.: J. biol. Chem. 235, 1634 (1960).Google Scholar
- 27.Hollis, V.W., Jr., Tomkins, G.M.: J. biol. Chem. 235, 3112 (1960).Google Scholar
- 28.Tomkins, G.M.: Fed. Proc. 19, 29 (1960).Google Scholar
- 29.Wilton, D.C., Ringold, H.J.: Proceedings of the Third International Congress on Endocrinology, Mexico City, 1968, p. 105.Google Scholar
- 32.Advanc. Biosci. 2, 69 (1969).Google Scholar
- 36.Adachi, K., Kano, M.: Biochem. biophys. Res. Commun. 41, 884 (1970).Google Scholar