Endocrine Abstracts

Topical glucocorticoid therapy causes adverse effects in human skin including a reduction in dermal fibroblast proliferation and extracellular matrix protein secretion (e.g. collagen 1) and epidermal thinning – effects paralleled in photoexposed and elderly skin. These cause reduced wound healing rates and a loss of elasticity with increased fragility and transepidermal water loss – signs also typical of Cushing’s syndrome characterised by raised circulating cortisol levels.

Locally, cortisol concentrations are maintained, in part, by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), activating cortisol from cortisone in an NADPH-dependant manner.

We aimed to determine the location of 11β-HSD1 in skin, the baseline levels of expression in cells derived from donors of variable age, it’s regulation by dexamethasone and functional implications on markers of skin integrity such as collagen 1 and matrix metalloproteinases.

Sections of skin were antibody-labelled and localized 11β-HSD1 to dermal fibroblasts and epidermal keratinocytes. Expression by real-time PCR was 17-fold greater in primary fibroblasts derived from older donors (Mean ΔC_t ±S.D. 20.9±0.8 age 47–78 n=6 vs 25.4±1.1 age 21–35 n=6, P<0.001) independently of gender and body site. 24 h treatment with 100nM dexamethasone increased expression (2.5-fold, P<0.01) in fibroblasts from photoexposed (n=7), but not photoprotected (n=4) samples. This translated to a 6-fold increase in activity measured by radioactive substrate conversion.

The increase in 11β-HSD1 with age may contribute to age-associated deterioration in skin function and morphology, such as decreasing collagen 1 levels, by locally increasing cortisol concentrations. Additionally, upregulation by dexamethasone specifically in photoexposed site-derived fibroblasts may further exacerbate the adverse effects associated with UV exposure.