Responsiveness to Androgens and Effectiveness of Antisense Oligonucleotides against the Androgen Receptor on Human Epidermal Keratinocytes is Dependent on the Age of the Donor and the Location of Cell Origin

S. Fimmel; R. Kurfurst; F. Bonté; C. C. Zouboulis

doi:10.1055/s-2007-961810

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2007; 39(2): 157-165
DOI: 10.1055/s-2007-961810

Original

Responsiveness to Androgens and Effectiveness of Antisense Oligonucleotides against the Androgen Receptor on Human Epidermal Keratinocytes is Dependent on the Age of the Donor and the Location of Cell Origin

S. Fimmel¹ , R. Kurfurst² , F. Bonté² , C. C. Zouboulis¹ ^, ³

¹Laboratory of Biogerontology, Dermato-Pharmacology and Dermato-Endocrinology, Institute of Clinical Pharmacology and Toxicology, Campus Benjamin Franklin, Charité Universitaetsmedizin Berlin, Berlin, Germany
²LVMH Research, St Jean de Braye, France
³Departments of Dermatology and Immunology, Dessau Medical Center, Dessau, Germany

Abstract

Local androgen excess has been associated with attenuation of wound healing in elderly individuals and with a decline in permeability barrier homeostasis in adult human skin. In this study we have applied specific antisense oligonucleotides, whose activity has already been investigated in SZ95 sebocytes, to inactivate transiently the androgen receptor in a reconstituted epidermis model and in primary human epidermal keratinocytes of different origin (breast, abdomen, foreskin) and donor age (females, 30- and 60-year-old). Further a possible interaction between blockage of androgen receptor and the expression of tissue inhibitors of matrix metalloproteinases was investigated. Androgen receptor levels were similar in pooled keratinocytes of the two age groups. Cell transfection with antisense oligonucleotides against the androgen receptor resulted in decreasing protein levels detected in all epidermal keratinocytes tested, whereas cells of aged donors (60-year-old) exhibited a stronger response than cells of young individuals (30-year-old). Keratinocytes from aged donors also responded to androgens with a stronger regulation of proliferation than keratinocytes of young individuals. The pattern of the androgen-induced response was dependent on the skin region of keratinocyte origin. The expression levels of tissue inhibitor of matrix metalloproteinase-1 were not age-related. Our results demonstrate an enhanced androgen sensitivity of keratinocytes from aged individuals associated with an origin-specific type of response.

Key words

antisense oligonucleotides - epidermis model - androgen - aging - TIMP-1

Full Text

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Correspondence

C. C. Zouboulis

Departments of Dermatology and Immunology

Dessau Medical Center

Auenweg 38

06847 Dessau

Germany

Phone: +49340501 40 00

Fax: +49340501 40 25

Email: christos.zouboulis@klinikum-dessau.de