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.