Cortisol-4-[ l e ] was found actively metabolized by slices of human skin. By paper chromatography, isotopic dilution, and the preparation of acetates, the following metabolites were identified: cortisone, Ad-pregnene-1 1&17cr,2Op,21 -tetraol-3-one (Reichstein's substances E), A4-pregnene-1 lp-17cu,20a,21-tetraol-3-one (epi-E), A4-pregnene-17a-2OP,21-triol-3,1l-dione (U), and A4-pregnene-17a,20a,21-triol-3,1 1-dione (epi-A previous communication from this laboratory presented evidence of active metabolism of cortisol-4-[lC] by slices of human skin (Hsia et al., 1964). Several metabolites were detected by paper chromatography; it was also noticed that one of the peaks of radioactivity in the paper chromatogram was characteristic of the metabolism of foreskin and was not detected after incubation with skin of other anatomical sites. That the metabolism is linked to the pyridine nucleotides was demonstrated in a subsequent study Wsia et ul., 1965) in which skin specimens obtained at autopsy were found to have lost their ability to metabolize cortisol, but the metabolism could be restored by the addition of TPNH1 or DPNH to the incubation medium. In the same study it was found that both the dermis and epidermis are capable of metabolizing Cortisol. 'The following abbreviations and trivial names are used: TPN+ and TPNH, oxidized and reduced triphosphopyridine nucleotide; DPNH, reduced diphosphopyridine nucleotide ; cortisol, Ad-pregnene-1 lp,17a,21-triol-3,20-dione; cortisone, A L pregnene-17a,21-dio1-3,11,20-trione; allodihydrocortisot. Sa. pregnane-llp,17a,2l-triol-3,20-dione; allotetrahydrocortisol, Sapregnane-3a, 11,9,17a,21-tetraol-20-one; dihydrocortisol. SB-pregnane-l1~.17a,21-triol-3,20-dione; tetrahydrocortisol (THF), 5p-pregnane~3a,ll~,l7a,2l-tetraol-20-one: tetrahydrocortisone (THE), 5,9-pregnane-3a,17a,2l-triol-l1,20-dione; Reichstein's substances E, A cpregnene-1 lp,17a,20& 2 1-tetraol-3-one ; epi-E, A 4-pregnene-1 1&17~,20a,21-tetraol-3-one ; U, A cpregnene-17a,-20&2 1 -triol-3,ll-dione ; epi-U, A '-pregnene-17a,ZOa,21-triol-3,ll-dione. U), allodihydrocortisol, and allotetrahydrocortisol. The latter two steroids were found only after incubation of cortis014-[~4C] with foreskin and not with skin of other anatomical sites. The two general pathways of metabolism of cortisol in human skin appear to be oxidation of the llp-01 and reduction of the 20-one while saturation of the Ad-double bond and reduction of the 3-one appear limited to the foreskin.In a continuation of these studies, several metabolites have now been identified, including cortisone and Reichstein's substances E, epi-E, U, and epi-U. Allodihydrocortisol and allotetrahydrocortisol have been found, so far, only after incubation of cortisol with foreskin; their formation after incubation with skin of other anatomical sites could not be established. The evidence for the identification of these metabolites is reported in this paper.
Experimental Section and ResultsMaterials. Cortisol-4-[ I C ] with specific activity of 22.5 mc/mmole was purchased f...