Biochemical study of testosterone in skin: in vivo and in vitro metabolism of testosterone in rat skin.

In vitro and in vivo testosterone metabolism was studied using rat skin. The in vitro stoichiometric studies strongly suggested the existence in the skin of 5a-reductase and other enzymes involved in testosterone metabolism. The predominant metabolites were 5adihydrotestosterone, androstandiol and 6.4-androstenedione. The rate of testosterone metabolism in vitro was higher in preputial skin than in dorsal skin. The main metabolites were androstandiol and 6 4androstenedione in vivo whereas dihydrotestosterone and androstandiol were predominant in vitro. .6.4-Pathway is considered to be more active in vivo in adults than in newborns. The difference in the in vivo uptake increase of testosterone-3H after castration suggests the possible existence in the organs and skin areas of androgen pools of different sizes. The in vivo uptake and metabolism of testosterone were examined in the nuclei of newborn rats. Dihydrotestosterone and androstandiol detected in the nuclei of preputial skin, dorsal skin and liver were 42.8%, 24.3% and 27.8%, of total radioactivity incorporated into the respective organs. The liver incorporated only a small amount of radioactivity compared with the skin. ∗PMID: 143191 [PubMed indexed for MEDLINE] Copyright c ©OKAYAMA UNIVERSITY MEDICAL SCHOOL Acta Med. Okayama 31, 129-139 (1977) BIOCHEMICAL STUDY OF TESTOSTERONE IN SKIN: IJ.V VIVO AND IN VITRO METABOLISM OF TESTOSTERONE IN RAT SKIN Masaharu HAGIYAMA Department of Dermatology, Okayama University Medical School, Okayama 700, Japan (Director.' Prof. N. Nohara) Received January 26, 1977 Abstract. In vitro and in vivo testosterone metabolism was studied using rat skin. The in vitro stoichiometric studies strongly suggested the existence in the skin of 5a-reductase and other enzymes involved in testosterone metabolism. The predominant metabolites were 5adihydrotestosterone, androstandiol and 6.4-androstenedione. The rate of testosterone metabolism in vitro was higher in preputial skin than in dorsal skin. The main metabolites were androstandiol and 6 4-androstenedione in vivo whereas dihydrotestosterone and androstandiol were predominant in vitro. .6.4-Pathway is considered to be more active in vivo in adults than in newborns. The difference in the in vivo uptake increase of testosterone-3H after castration suggests the possible existence in the organs and skin areas of androgen pools of different sizes. The in vivo uptake and metabolism of testosterone were examined in the nuclei of newborn rats. Dihydrotestosterone and androstandiol detected in the nuclei of preputial skin, dorsal skin and liver were 42.8%, 24.3% and 27.8%, of total radioactivity incorporated into the respective organs. The liver incorporated only a small amount of radioactivity compared with the skin. In vitro and in vivo testosterone metabolism was studied using rat skin. The in vitro stoichiometric studies strongly suggested the existence in the skin of 5a-reductase and other enzymes involved in testosterone metabolism. The predominant metabolites were 5adihydrotestosterone, androstandiol and 6.4-androstenedione. The rate of testosterone metabolism in vitro was higher in preputial skin than in dorsal skin. The main metabolites were androstandiol and 6 4-androstenedione in vivo whereas dihydrotestosterone and androstandiol were predominant in vitro. .6.4-Pathway is considered to be more active in vivo in adults than in newborns. The difference in the in vivo uptake increase of testosterone-3H after castration suggests the possible existence in the organs and skin areas of androgen pools of different sizes. The in vivo uptake and metabolism of testosterone were examined in the nuclei of newborn rats. Dihydrotestosterone and androstandiol detected in the nuclei of preputial skin, dorsal skin and liver were 42.8%, 24.3% and 27.8%, of total radioactivity incorporated into the respective organs. The liver incorporated only a small amount of radioactivity compared with the skin. The skin has been thought to be one of the target organs of testosterone (T). Several specific metabolites of T have been identified using the whole rat skin (1) and rat preputial gland (2). Since dihydrotestosterone is the most potent androgen in the prostate, this suggests that the mode of action of T in the skin (3, 4) is related to 5a-reductase. However, there is no well established study on the relationship between 5[l'reductase and the presence of T in the skin. Much additional work remains to be done to clarify not only the specific pathway of T metabolism but physiological significance of T and 5a-reductase in the skin. MATERIALS AND METHODS Chemicals. Testosterone-4-14C (specific activity 52.8,uCi/,u mole) was purchased from New England Nuclear Corp., and checked for purity by thin layer chromatography in a ligroin-propylene glycol system. A methanolic stock solution containing 1.1 X 106 cpm (9.5 n moles) in each 0.1 ml was prepared and stored at -20°C. 5a-Dihydro-(la,2a (n)-3H)-testosterone (40,000-60,000 mCi/m mole), 129 1 Hagiyama: Biochemical study of testosterone in skin: in vivo and in vitro Produced by The Berkeley Electronic Press, 1977