Testosterone metabolism by human male mammary skin

Rongone, Edward L.

doi:10.1016/0039-128x(66)90139-5

Cited by 39 publications

(15 citation statements)

References 4 publications

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“…The mean values (in liters/gram of serum protein) were, respectively, 1.56 +0.59 SE for testicular feminization syndrome cases (n = 6 determinations), 0.90 0.21 SE is 2 times higher than that originating from testosterone which enters the liver directly by the portal vein, whereas the yield of androstanediol arising from testosterone percutaneously applied is 2.5 times higher than that arising from testosterone injected in the peripheral circulation. These results are in agreement with in vitro data suggesting that a characteristic of cutaneous testosterone metabolism is the stereospecific reduction of the ring A leading to the formation of 5a-androstane steroids (18,19). The actual importance of testosterone metabolism by an organ as large as the skin is difficult to establish.…”

Section: Introductionsupporting

confidence: 86%

Studies on testosterone metabolism in subjects with testicular feminization syndrome

Mauvais-Jarvis¹,

Bercovici²,

Crépy³

et al. 1970

J. Clin. Invest.

115

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A B S T R A C T The metabolism of radioactive testosterone simultaneously administered intravenously and either orally or percutaneously has been studied in seven patients with the syndrome of testicular feminization and compared with that of normal males and females. This investigation was carried out in order to determine the relative contribution to urinary 17-oxo and 17p-hydroxy androstane steroids of labeled testosterone, according to its mode of administration. In normal males the yields of urinary 5a-androstane-3a,17,-diol (androstanediol) originating from either an intravenous or a percutaneous dose of testosterone were respectively 3 and 6 times higher than those arising from an oral dose which perfuses the liver directly. These data indicate that in normal males, testosterone might be 5a-hydrogenated outside the liver. By contrast in patient with feminizing testes, because the contribution to androstanediol of radioactive testosterone is identical whatever its mode of administration, the extrahepatic 5a-reduction of this substrate seems very unlikely.The metabolic abnormalities observed in patients with testicular feminization syndrome may be reproduced in normal males by estrogen treatment. Nevertheless, the sensitivity of the patients to estrogen seems to be 10 times greater than that of normal males. This sensitivity was appreciated from the reduction of radioactive testosterone intravenously injected to urinary 17P-hydroxy-5a-androstan-3-one and androstanediol and also from the level of plasma binding for testosterone. This level was significantly higher (P < 0.05) in patients with feminizing testes than in normal males. The level increased dramatically after administration of a low dose of estrogen whereas this effect was not observed in normal males under the same experimental conditions.In light of these results the defect of extrahepatic 5a-reduction of testosterone observed in patients with Part of this work has been published as a preliminary communication (14).

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Section: Introductionsupporting

confidence: 86%

Studies on testosterone metabolism in subjects with testicular feminization syndrome

Mauvais-Jarvis¹,

Bercovici²,

Crépy³

et al. 1970

J. Clin. Invest.

115

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“…5p-reductasc activity may also be present since a band which comigrated with 5p-DHT was detected in the second solvent system employed [26]. Although the presence of 5p-DHT in skin has been occasionally reported [7,8], the occurrence of 5p-DHT in the LSE is not definitive based on runs in this single sol vent system.…”

Section: Discussionmentioning

confidence: 93%

Absorption and Metabolism of Topically Applied Testosterone in an Organotypic Skin Culture

Ernesti

Swiderek²

1992

Skin Pharmacol Physiol

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The Living Skin Equivalent (LSE^TM) is an organotypic coculture of human dermal fibroblasts in a collagen-containing matrix and a stratified epidermis composed of human epidermal keratinocytes. In order to establish the feasibility of using this in vitro system as a model for cutaneous biotransformation, the metabolic fate of topically applied testosterone (T) was monitored in the LSE. After a 24-hour exposure period (37 °C) to radiolabelled T, LSE extracts analyzed by high-performance thin-layer chromatography showed that approximately 50% of the applied T had been metabolized. Identified metabolites included bands which comigrated with polar metabolites and products of T 5Α-reductase. The general distribution of the observed metabolites was similar to that obtained usingbiopsied human skin. The rates of T penetration (32 °C) through the LSE were monitored after application of T in two vehicles (water and petrolatum) and yielded permeability constants (Kps) of 29 and 1.6 × 10^-3 cm/h, respectively. These Kp values were 4- to 6-fold higher than those reported for human abdominal skin, and reflect the vehicle-related shift in penetration seen in human skin. The Kp values for two additional steroids, estradiol and hydrocortisone, and for T were also determined at 22 °C and compared to published Kp values. These Kp values in the LSE were, respectively, 63-, 187-and 35-fold higher than those reported for human skin. The data suggest that compared to human skin the LSE has only a partial barrier function to the passage of test chemicals. The magnitude of the difference in the rates of penetration between the LSE and human skin depends on the test chemical. For specific chemicals, such as T, the LSE simulates certain aspects of skin metabolism and percutaneous absorption.

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“…This somewhat unexpected finding made us consider that some aspects of testosterone production or clearance in addition to plasma levels may be of significance in the development of hirsutism. The recent reports of testosterone metabolism by skin (14) may be pertinent to the clearance of testosterone, but meaningful estimates of the fraction of testosterone metabolized by skin cannot be made as yet.…”

Section: Discussionmentioning

confidence: 99%

Testosterone and Androstenedione Blood Production Rates in Normal Women and Women with Idiopathic Hirsutism or Polycystic Ovaries*

Bardin¹,

Lipsett²

1967

J. Clin. Invest.

323

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Summary. The average plasma testosterone concentration of women with either hirsutism or polycystic ovaries and hirsutism was higher (p < 0.01) than that of normal women although the ranges overlapped. Testosterone blood production rates averaged 830 ± 120 SE and 1,180 ± 310 SE ,ug per day in the two groups of hirsute women and 230 ± 33 SE ,ug per day in normal women. The ranges did not overlap.The testosterone metabolic clearance rates of hirsute women (1,090 ± 140 SE L per day) and of men (1,240 + 136 SE L per day) were significantly higher than those of normal women (590 + 44 SE L per day). These differences persisted when the metabolic clearance rates were corrected for surface area. We suggest that testosterone metabolic clearance rates vary directly with some function of testosterone production.The mean plasma androstenedione levels (2.8 ± 0.35 SE and 2.8 + 0.30 SE ,ug per L) and production rates (6,060 ± 450 SE and 7,360 + 345 SE ,ug per day) of the women with hirsutism or polycystic ovaries, respectively, were significantly higher than those of normal women (1.5 + 0.22 SE pg per L; 3,300 + 830 SE pg per day). The androstenedione metabolic clearance rates were the same in each group. Plasma androstenedione was the precursor of 49% of plasma testosterone in normal women and of 26% of plasma testosterone in hirsute women. Thus, 74% of the plasma testosterone in these subjects must have been either secreted or derived from a precursor that did not enter the plasma androstenedione pool.

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Testosterone metabolism by human male mammary skin

Cited by 39 publications

References 4 publications

Studies on testosterone metabolism in subjects with testicular feminization syndrome

Studies on testosterone metabolism in subjects with testicular feminization syndrome

Absorption and Metabolism of Topically Applied Testosterone in an Organotypic Skin Culture

Testosterone and Androstenedione Blood Production Rates in Normal Women and Women with Idiopathic Hirsutism or Polycystic Ovaries*

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