Dose-response Effects of Tri-iodothyroacetic Acid (Triac) and Other Thyroid Hormone Analogues on Glucocorticoid-Induced Skin Atrophy in the Haired Mouse

Abstract

Thyroid hormones have an in uence on the connectivedermal blood ow as a consequence of increased metatissue biology of the skin and, theoretically, topically bolic rate and decreased systemic vascular resistance applied thyroid hormones or hormone analogues could have and are thus not attributable to a direct action of TH a stimulatory eVect on collagen synthesis. In this investion cells in the skin (2-5). However, it is also known gation the eVect of topical tri-iodothyroaceti c acid (Triac) that the connective tissue biology of the skin is sensitive and other thyroid hormone analogues were tested for their to alterations in thyroid hormone status (3) and the eVect in preventing betamethasone-indu ced skin atrophy in presence of intracellular receptors ( TRs) for thyroid the normal haired mouse. Triac, tri-iodoproprioni c acid hormones in human skin, in both dermal and epidermal ( Triprop) and the synthetically developed thyroid hormone parts, have been demonstrate d (6-10). analogue KB-026 and 2 diVerent Triac cream formulationsInformation concerning the mechanism of action of TH were applied along with betamethasone on shaved mouse in broblasts, especially in regulation of collagen producskin. Triac in daily doses of 1 nmol/cm2 and higher was tion, is limited. In one study by Rycker et al., thyroid able to block the betamethasone-induce d skin atrophy in hormone administration diminished collagen production mice skin. In high doses, Triprop and KB-026 also had a in cultured broblasts (9). Although a vast number of blocking eVect. Triac alone had a stimulatory eVect on studies on thyroid hormone action in organs such as liver, dermal thickness. This study indicates that thyroid hormone heart, pituitary, brain and adipose tissue have been peranalogues may be used to prevent corticosteroid-induce d formed, no studies have been undertaken to investigate skin atrophy. Keywords: animal model; skin thickness; the activity of topical TH in glucocorticoid-treated skin. normal haired mouse.Moreover, as TRs are part of a larger superfamily of nuclear receptors, which comprises the receptors for gluco-

11β-Hydroxysteroid dehydrogenase blockade prevents age-induced skin structure and function defects

“…GC treatment of primary HDFs decreased collagen transcription (1) and altered collagen metabolizing enzymes (7) as previously shown. We found additional GC targets, including reduced expression of collagen posttranslational hydroxylation enzymes (3), collagen chaperone (4), and all lysyl oxidase enzyme isoforms required for collagen inter-and intrafibril cross-link formation (6). Nephew) and Hypafix tape (BSN Medical).…”

“…In skin, GC excess leads to marked atrophy with dermal and epidermal thinning according to both human (2-4) and rodent (5,6) studies. GCs also induce a flattening of the normally undulating "rete ridges" at the dermal-epidermal junction (DEJ) (7).…”

Thyroid hormones and the control of cell proliferation or cell differentiation: Paradox or duality?

“…In vivo, topical T3 stimulates epidermal proliferation, dermal thickening and hair growth (Safer et al, 2001;Safer et al, 2003;Safer, 2005). Topical triac (tri-iodothyroacetic acid) thickens skin by stimulating the production of collagen (Faergemann et al, 2002;Yazdanparast et al, 2004). However, TH effects on skin depend on the route of delivery.…”

Triiodothyroacetic acid in health and disease

“…Topical application of TA 3 increases dermal thickness and prevents glucocorticoid-induced skin atrophy in mice and humans (Faergemann et al 2002, Yazdanparast et al 2006a, and stimulates procollagen synthesis and keratinocyte proliferation in human skin (Yazdanparast et al 2004, Zhang et al 2012, but has no beneficial effects on plaque psoriasis (Vahlquist et al 2004). …”