title: The thyroid hormone degrading type 3 deiodinase is the primary deiodinase active in murine epidermis.
abstract: BACKGROUND
  Many tissues express thyroid hormone metabolizing deiodinases that both activate and inactivate thyroid hormones through conversion processes. Many believe that the primary role of thyroid hormone deiodinases is the activation of the prohormone thyroxine (T(4)) to the active hormone triiodothyronine because athyreotic humans can be treated with T(4) alone. In our hands a nonspecific deiodinase inhibitor (iopanoic acid [IOP]) decreased cutaneous cell proliferation in vitro, so we hypothesized that topical IOP would inhibit epidermal proliferation in vivo.
  
  
  METHODS
  IOP was applied topically to mice. Treatments were applied daily for 1 week. Skin biopsies were either stained for 5-bromo-2-deoxyuridine or flash-frozen to assay for deiodinase activity.
  
  
  RESULTS
  Topical IOP resulted in a dose-dependent increase in epidermal proliferation. Assay revealed significant inactivating type 3 deiodinase (Dio3) activity in the epidermis but little or no activating (Dio1 or Dio2) activity. Dio3 activity was decreased 44%±21% in epidermis from mice treated with low-dose IOP and 80%±4% in epidermis from mice treated with high-dose IOP (p<0.001).
  
  
  CONCLUSIONS
  We hypothesize that keratinocytes express Dio3 in vivo to maintain cutaneous health and prevent the skin from becoming hyperproliferative. Our data support the developing recognition that the primary role of thyroid hormone deiodinases in some tissues may be the degradation of thyroid hormone to protect the tissue against thyrotoxicosis.
authors.affiliation: Section of Endocrinology, Diabetes, and Nutrition, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors.forename: Max P
authors.initials: MP
authors.lastname: Huang
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Rodgers
authors.forename: Rosemary
authors.initials: R
authors.lastname: O'Mara
authors.forename: Meetal
authors.initials: M
authors.lastname: Mehta
authors.forename: Hilal S
authors.initials: HS
authors.lastname: Abuzahra
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Tannenbaum
authors.forename: Kelly
authors.initials: K
authors.lastname: Persons
authors.forename: Michael F
authors.initials: MF
authors.lastname: Holick
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Safer
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004817:Epidermis / Q000201:enzymology*; D007453:Iodide Peroxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007480:Iopanoic Acid / Q000494:pharmacology; D051379:Mice; D008812:Mice, Hairless; D013974:Thyroxine / Q000378:metabolism
chemical_list: C117274:iodothyronine deiodinase type III; D007453:Iodide Peroxidase; D007480:Iopanoic Acid; D013974:Thyroxine