Authors: Makrantonaki, E.; Zouboulis, C.C.

Source: British Journal of Dermatology, Volume 156, Number 3, March 2007 , pp. 428-432(5)

Publisher: Wiley-Blackwell

Abstract:

Summary Background 

Despite the clinical evidence that androgens stimulate sebaceous lipids, androgens in vitro have shown no similar effects. This contradiction led to the assumption that cofactors may be required for lipid regulation and peroxisome proliferator-activated receptor (PPAR) ligands were suggested to be adequate candidates. Objectives 

The influence of testosterone and linoleic acid, a PPAR ligand, as single agents and in combination with of LY191704, a 5α-reductase type I inhibitor, was examined on 5α-dihydrotestosterone (5α-DHT) synthesis and lipid content in human SZ95 sebocytes. Methods 

Cell proliferation and viability were measured by the 4-methylumbelliferyl heptanoate fluorescence assay and by the Boehringer Lactate Dehydrogenase Assay kit, respectively. 5α-DHT enzyme-linked immunosorbent assay was used for the detection of 5α-DHT synthesis in cell supernatants after treatment, whereas lipid production was documented by means of the Nile red lipid microassay and fluorescence microscopy. Results 

Testosterone promoted 5α-DHT synthesis (P < 0·001), whereas linoleic acid increased sebaceous lipids (P < 0·001). The combination of testosterone and linoleic acid exhibited a synergistic effect on the synthesis of 5α-DHT (P < 0·01 vs. testosterone) and sebaceous lipids (P < 0·01 vs. linoleic acid). Furthermore, LY191704 reduced 5α-DHT and sebaceous lipid levels (P < 0·01 and P < 0·001 in comparison with testosterone/linoleic acid, respectively). Cell proliferation and viability remained unchanged under treatment with all compounds tested. Conclusions 

These data suggest a catalytic effect of PPAR ligands on cellular testosterone activation by 5α-reduction and the importance of the latter for the regulation of sebaceous lipids.

Keywords: 5α-reductase inhibitor; androgens; lipids; peroxisome proliferator-activated receptors; sebocytes

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-2133.2006.07671.x

Affiliations: 1: Laboratory of Biogerontology, Dermatopharmacology and Dermatoendocrinology, Institute of Clinical Pharmacology and Toxicology, Charité University Medicine Berlin, Campus Benjamin Franklin, Garystrasse 5, 14195 Berlin, Germany

Publication date: 2007-03-01

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