bromochloroacetic-acid and Hypothyroidism

Retinoids play an important role in skin homeostasis and when administered topically cause skin hyperplasia, abnormal epidermal differentiation and inflammation. Thyroidal status in humans also influences skin morphology and function and we have recently shown that the thyroid hormone receptors (TRs) are required for a normal proliferative response to 12-O-tetradecanolyphorbol-13-acetate (TPA) in mice.. We have compared the epidermal response of mice lacking the thyroid hormone receptor binding isoforms TRα1 and TRβ to retinoids and TPA. Reduced hyperplasia and a decreased number of proliferating cells in the basal layer in response to 9-cis-RA and TPA were found in the epidermis of TR-deficient mice. Nuclear levels of proteins important for cell proliferation were altered, and expression of keratins 5 and 6 was also reduced, concomitantly with the decreased number of epidermal cell layers. In control mice the retinoid (but not TPA) induced parakeratosis and diminished expression of keratin 10 and loricrin, markers of early and terminal epidermal differentiation, respectively. This reduction was more accentuated in the TR deficient animals, whereas they did not present parakeratosis. Therefore, TRs modulate both the proliferative response to retinoids and their inhibitory effects on skin differentiation. Reduced proliferation, which was reversed upon thyroxine treatment, was also found in hypothyroid mice, demonstrating that thyroid hormone binding to TRs is required for the normal response to retinoids. In addition, the mRNA levels of the pro-inflammatory cytokines TNFα and IL-6 and the chemotactic proteins S1008A and S1008B were significantly elevated in the skin of TR knock-out mice after TPA or 9-cis-RA treatment and immune cell infiltration was also enhanced.. Since retinoids are commonly used for the treatment of skin disorders, these results demonstrating that TRs regulate skin proliferation, differentiation and inflammation in response to these compounds could have not only physiological but also therapeutic implications.

Topics: Alitretinoin; Animals; Blotting, Western; Cell Differentiation; Cell Proliferation; Cyclin-Dependent Kinase Inhibitor p21; Epidermis; Female; Hyperplasia; Hypothyroidism; Interleukin-6; Keratins; Lymphocytes; Macrophages; Male; Mice; Mice, Knockout; Retinoids; Reverse Transcriptase Polymerase Chain Reaction; Skin; Tetradecanoylphorbol Acetate; Thyroid Hormone Receptors alpha; Thyroid Hormone Receptors beta; Tretinoin; Tumor Necrosis Factor-alpha

The importance of thyroid hormone (TH) in wound healing is not well understood. To gain insight, we evaluated the impact of TH deficiency on wound-healing genes in cultured keratinocytes. By RT-PCR, keratin 6a (K6a) and 16 (K16) gene expression in TH replete cells was 3.8- (P < 0.005) and 1.9-fold (P < 0.05) greater, respectively, than expression in TH-deficient cells. By real-time PCR, TH replete cell expression of K6a, K16, and K17 was greater than in deficient cells: 18- (P < 0.001), 10- (P < 0.001), and 4-fold (P < 0.005), respectively. To examine TH requirement for optimal wound healing, we contrasted TH-deficient vs. ip T(3)-treated mice. Four days after wounding, ip T(3)-treated mice had twice the degree of wound closure as hypothyroid mice (P < 0.001). By RT-PCR, K6a and K17 gene expression from control mouse skin was greater than from hypothyroid mouse skin: 5- (P < 0.001) and 1.7-fold (P < 0.05), respectively. T(3) is necessary for the keratinocyte proliferation required for optimal wound healing. T(3) exerts influence by stimulating expression of the wound-healing keratin genes. Thus, for hypothyroid patients undergoing surgery that cannot be delayed until euthyroidism is achieved, our data support T(3) treatment for the perioperative period.

Topics: Animals; Cell Division; Cells, Cultured; Gene Expression; Humans; Hypothyroidism; Keratinocytes; Keratins; Mice; Polymerase Chain Reaction; Thyroidectomy; Triiodothyronine; Wound Healing

Topics: Animals; Animals, Newborn; Eyelids; Female; Hypothyroidism; Injections, Intraperitoneal; Keratins; Maternal-Fetal Exchange; Morphogenesis; Pregnancy; Rats; Receptors, Cell Surface; Thiouracil; Thyroxine

Topics: Alopecia; Biomechanical Phenomena; Elasticity; Female; Genetic Diseases, Inborn; Hair; Homocystinuria; Humans; Hyperthyroidism; Hypothyroidism; Ichthyosis; Keratins; Keratosis; Male; Oxidation-Reduction; Skin Diseases; Ultrasonography; X-Ray Diffraction