Hydroxylation of leukotriene B4 in leukocytes from various species: identification of a metabolite to authentic 5S,12R,19-trihydroxy-6Z,8E,10E,14Z-eicosatetra enoic acid and relative importance of 19- and 20-hydroxylations

The major hydroxylated metabolite of leukotriene B4 in rat PMNL was found identical (UV spectrum and retention times in 3 different HPLC systems) to a synthetic compound of known stereochemistry, 19-hydroxy-LTB4. PMNL from various species exhibited 3 different types of behaviour for LTB4 hydroxylation. Human and monkey PMNL showed a high hydroxylating activity and a high regioselectivity with almost exclusive formation of products from 20-hydroxylation. Rat and mini-pig PMNL exhibited a very different regioselectivity with major formation of 19-OH-LTB4 (3:1 ratio). Finally, pig and beef PMNL were found almost devoid of any hydroxylating activity toward LTB4.     

Pangenomic changes induced by DHEA in the skin of postmenopausal women

The objective of this study was to explore, for the first time, the changes in the pangenomic profile induced in human skin in women treated with dehydroepiandrosterone (DHEA) applied locally.Sixty postmenopausal women participated in this phase II prospective, randomized, double-blind and placebo-controlled study. Women were randomized to the twice daily local application of 0% (placebo), 0.3%, 1% or 2% DHEA cream. Changes in the pangenomic expression profile were studied using Affymetrix Genechips.Significant changes (p < 0.05) in sixty-six DHEA-responsive probe sets corresponding to 52 well-characterized genes and 9 unknown gene sequences were identified. A dose-dependent increase in the expression of several members of the collagen family was observed, namely COL1, COL3 and COL5 as well as the concomitant modulation of SPARC, a gene required for the normal deposition and maturation of collagen fibrils in the dermis. Several genes involved in the proliferation and differentiation of keratinocytes were also modulated. In addition, topical DHEA reduced the expression of genes associated with the terminal differentiation and cornification of keratinocytes.Our results strongly suggest the possibility that DHEA could exert an anti-aging effect in the skin through stimulation of collagen biosynthesis, improved structural organization of the dermis while modulating keratinocyte metabolism.