Action of topical thyroid hormone analogues on glucocorticoid-induced skin atrophy in mice.

Previously we demonstrated the stimulation of collagen synthesis in triiodothyroacetic acid (TRIAC)-topically treated human and mice. In the present study, we have evaluated the dose response effect of thyroid hormone (TH) analogues and tretinoin on glucocorticoid-induced skin atrophy in a haired mouse model. For this investigation, we treated haired mice twice daily for 7 days with various topically administered doses of TRIAC, triiodothyronine-sodium salt (T(3)-Na), diiodothyroacetic acid (DIAC), 3,5-diiodothyropropionic acid (DITPA), and tretinoin with 0.2 mM betamethasone17-valerate (BM), or with the vehicle as a control group. We also investigated a combination of commercial betamethasone dipropionate (BD) 0.05% cream and various doses of TRIAC on mouse skin. TRIAC was able to reverse the skin atrophy by 25% in a daily dose of 1 nmol/cm(2) in the presence of 0.2 mM BM (p < 0.05). Neither other TH analogues nor TRIAC in lower and higher concentrations had a significant inhibitory effect on dermal atrophy (p > 0.05). A combination of 0.2 mM BM and 10 nmol/cm(2) TRIAC was able to prevent dermal atrophy by 18%. The addition of TRIAC to 0.05% BD cream in a final concentration of 0.1% was able partially to reverse the dermal atrophy by 15% (p < 0.05). TRIAC alone in a concentration of 1,000 nmol/cm(2) stimulated dermal proliferation by 34% (p < 0.05). Other TH analogues alone had no stimulatory effect on dermal proliferation. Tretinoin 0.8 mM was able to inhibit dermal atrophy by 20% (p < 0.05) and had an effect on dermal thickness of 85% (p < 0.05). However, severe side effects with edema, erythema, and scaling were commonly observed in all tretinoin-treated mouse skin, which could partly explain the increase in dermal thickness. In contrast, no skin side effects were observed after treatment with TRIAC. This study indicates that TRIAC may have a therapeutic effect on BM-induced dermal atrophy in mouse skin and a direct stimulatory effect on dermal proliferation when given alone.

Dose-response effects of tri-iodothyroacetic acid (Triac) and other thyroid hormone analogues on glucocorticoid-induced skin atrophy in the haired mouse.

Thyroid hormones have an influence on the connective tissue biology of the skin and, theoretically, topically applied thyroid hormones or hormone analogues could have a stimulatory effect on collagen synthesis. In this investigation the effect of topical tri-iodothyroacetic acid (Triac) and other thyroid hormone analogues were tested for their effect in preventing betamethasone-induced skin atrophy in the normal haired mouse. Triac, tri-iodoproprionic acid (Triprop) and the synthetically developed thyroid hormone analogue KB-026 and 2 different Triac cream formulations were applied along with betamethasone on shaved mouse skin. Triac in daily doses of 1 nmol/cm2 and higher was able to block the betamethasone-induced skin atrophy in mice skin. In high doses, Triprop and KB-026 also had a blocking effect. Triac alone had a stimulatory effect on dermal thickness. This study indicates that thyroid hormone analogues may be used to prevent corticosteroid-induced skin atrophy.