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Endocrine Abstracts (2015) 38 OC4.3 | DOI: 10.1530/endoabs.38.OC4.3

SFEBES2015 Oral Communications Diabetes and cardiometabolic complications (6 abstracts)

5α-tetrahydrocorticosterone exhibits topical anti-inflammatory action with limited adverse effects on angiogenesis

Annalisa Gastaldello , Dawn E Livingstone , Nicola Tsang , Brian R Walker , Patrick W Hadoke & Ruth Andrew

University of Edinburgh, Edinburgh, UK.

Background: The 5α-reduced glucocorticoid, 5α-tetrahydrocorticosterone (5α-THB), displays a dissociated steroid profile exhibiting anti-inflammatory effects in a murine model of thioglycollate-induced peritonitis but failing to induce adverse metabolic effects caused by corticosterone. We assessed the topical anti-inflammatory properties of 5α-THB in a model of irritant dermatitis. Given the adverse effects of steroids on cutaneous wound healing, we also investigated the anti-angiogenic properties of 5α-THB in vivo.

Methods: Ears of mice (n=10/group) were topically treated with irritant croton oil (CO, 300 μg) alone or with corticosterone (applied at EC50 dose, 5 μg) or 5α-THB (5, 15, and 25 μg) for 24 h. Swelling was assessed by ear weight at cull. To study angiogenesis, polyurethane sponges containing either 5α-THB (3 and 15 mg), corticosterone (3 mg), or vehicle, were implanted subcutaneously in mice (8–12/group) for 21 days. Newly formed vessels were analysed histologically; endothelial and smooth muscle cells and infiltrating macrophages were investigated immunohistochemically (CD31, αSMA, F4/80), and transcript profiles by qPCR. Data are mean±S.E.M., CO/vehicle group set to 100%, *P<0.05.

Results: 5α-THB decreased swelling similarly to corticosterone, but required a higher dose (25 μg 5α-THB, swelling reduced to 65±8%* vs 5 μg corticosterone, to 57±4%*). Corticosterone decreased the number of new vessels to 15±3%* whereas 5α-THB had less effect even at higher dose (3 mg, 87±13% NS; 15 mg, 46±7%*). While corticosterone inhibited both endothelial and smooth muscle cell recruitment (to 2±0.7 and 12±3%* respectively) and decreased transcripts of genes involved in angiogenesis and inflammation, 5α-THB inhibited only endothelial cell recruitment at high dose (15 mg, reduced to 20±5%*), without affecting the same transcripts. 5α-THB and corticosterone both attenuated the number of macrophages infiltrating the sponges (3 and 15 mg 5α-THB to 48±4% NS and 49±2*; corticosterone to 39±3%*). Importantly for repercussion on wound healing and skin homeostasis, 5α-THB unlike corticosterone did not decrease amount of collagen in sponges (3 and 15mg 5α-THB, changed to 106±16% NS and 128±20% NS vs corticosterone, 30±8%*).

Conclusions: 5α-THB displays the profile of a safer anti-inflammatory compound for topical application with limited effects on angiogenesis and extracellular matrix indicating it is less likely to impair wound healing or cause skin thinning.

Volume 38

Society for Endocrinology BES 2015

Edinburgh, UK
02 Nov 2015 - 04 Nov 2015

Society for Endocrinology 

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