A Thyroid Hormone Deiodinase Inhibitor Can Decrease Cutaneous Cell Proliferation In Vitro

Abstract

Although cutaneous manifestations associated with thyroid dysfunction are classic, the potential for thyroid hormone or its antagonists to treat dermatological disease has not been explored with rigor. The predominant circulating thyroid hormone is the pro-hormone, thyroxine (T(4)). Skin, like many tissues, expresses thyroid hormone deiodinases to convert T(4) to the active thyroid hormone, triiodothyronine (T(3)). Previously, we determined that T(3) is necessary for optimal growth of keratinocytes and fibroblasts. The first hypothesis of this experiment was that the deiodinase inhibitor iopanoic acid (IOP) could inhibit cutaneous cell proliferation. The second hypothesis of this experiment was that the action of IOP could be attributed to its inhibition of conversion of T(4) to T(3). Although IOP is known to inhibit T(4) to T(3) conversion, the inhibition of cutaneous cell proliferation by IOP might conceivably result from other properties of IOP. In separate experiments, primary culture human keratinocytes and dermal fibroblasts were incubated overnight with IOP. Proliferation was inhibited in a dose-dependent manner in both cell lines. Overnight incubation with T(3) restored the proliferation but overnight incubation with T(4) did not. The study is the first to demonstrate that IOP inhibits cutaneous cell proliferation and that supplemental T(3) is sufficient to correct at least part of the inhibition caused by IOP. The data suggest that IOP decreases cutaneous cell proliferation by inhibition of intracellular T(4) to T(3) conversion. The data provide indirect evidence of the presence of type 1 or type 2 iodothyronine deiodinase activity in skin cells. The data support our previous hypothesis that T(3) is necessary for normal cutaneous proliferation.