Swapna Ray

Topical Triiodothyronine Stimulates Epidermal Proliferation, Dermal Thickening, and Hair Growth in Mice and Rats

The skin is a classic target tissue for thyroid hormone action. Although the histology of skin in hypothyroid states is well documented, the literature contains little assessment of skin in thyrotoxic states. In light of the paucity of information on skin under the influence of excess thyroid hormone, we investigated the direct effect of thyroid hormone on skin. Triiodothyronine (T3) was applied topically daily in liposomes to SKH-1 hairless mice for 7 days and to CD rats for 2 weeks. There was a dose-dependent increase in epidermal proliferation, dermal thickening, and hair growth in T3-treated animals. Mice that received 3.8 microg of T3 had 42% more hairs per millimeter than controls (p < 0.01), hair length that was 1,180% longer (p < 0.001), 49% greater epidermal 3H-thymidine incorporation (p < 0.01), and 80% more 5-bromo-2-deoxyuridine (BrdU) stained cells (p < 0.05). Rats receiving 12.8 microg T3 had 48% greater dermal thickness than controls (p < 0.001), 26% greater epidermal thickness (p < 0.001), 85% more hairs per millimeter (p < 0.005), and 130% greater 3H-thymidine incorporation into the epidermis (p < 0.01). Thus, topically applied thyroid hormone has dramatic effects on both skin and hair growth. These observations offer a new strategy for developing thyroid hormone and its analogues for treating disorders of skin and hair growth.

Thyroid Hormone Action on Skin: Diverging Effects of Topical versus Intraperitoneal Administration

Previously, we demonstrated stimulation of epidermal proliferation and hair growth in triiodothyronine (T(3)) treated mice. To distinguish skin effects of directly applied T(3) from those of systemic hyperthyroidism, we treated CD-1 mice with either intraperitoneally (IP) or topically administered T(3). Relative to controls, mice receiving T(3) IP had 10% thinner epidermis (p < 0.01) and 48% fewer hairs (p < 0.001). By contrast, mice receiving T(3) topically had 78% thicker epidermis (p < 0.01) and 160% more hairs (p < 0.01). To gain insight into factors responsible for the diverging effects, we contrasted T(3) effect on proliferation of isolated keratinocyte cultures versus keratinocytes cocultured with dermal fibroblasts. For keratinocytes grown in the absence of fibroblasts, T(3) stimulated proliferation in a dose-dependent, biphasic pattern with the peak at 0.5 nM T(3) (84 +/- 30%, p < 0.05). Paradoxically, T(3) inhibited proliferation of keratinocytes cocultured with fibroblasts, the nadir at 0.1 nM T(3) (34% +/- 4%, p < 0.001). These studies are the first describing divergent effects of IP and topically administered thyroid hormone. The data suggest that while T(3) stimulated keratinocyte proliferation, T(3) also stimulated proliferation inhibitory factor(s) from skin fibroblasts. Insight into the interplay among the competing factors will be important in understanding thyroid hormone regulation of skin physiology.

Topical PTH (1-34) is a novel, safe and effective treatment for psoriasis: a randomized self-controlled trial and an open trial.

Summaryu2003 Backgroundu2003There continues to be a need to develop new pharmacological approaches for treating the common skin disease psoriasis. Human skin produces parathyroid hormone related peptide. This peptide is a potent inhibitor of epidermal cell growth.

Topical paricalcitol (19-nor-1α,25-dihydroxyvitamin D2) is a novel, safe and effective treatment for plaque psoriasis: a pilot study

Backgroundu2002 There continues to be a need to develop new pharmacological approaches for treating psoriasis. Topical active vitamin D compounds have proven to be both safe and effective for treating psoriasis. Paricalcitol (19‐nor‐1α,25‐dihydroxyvitamin D2) is a novel vitamin D analogue which has been developed for the prevention of secondary hyperparathyroidism in patients with chronic renal failure.

Photoaffinity labeling of chick intestinal 1α,25-dihydroxyvitamin D3 receptor ☆

Abstract The photoaffinity labeling of chick intestinal 1α,25-dihydroxyvitamin D 3 receptor with 1α,25-dihydroxyvitamin D 3 -3β-{N-(-4-azido-2-nitro[3,5- 3 H]phenyl)}glycinate has been determined under a variety of conditions .

Covalent labeling of nuclear vitamin D receptor with affinity labeling reagents containing a cross-linking probe at three different positions of the parent ligand: Structural and biochemical implications

Structure-functional characterization of vitamin D receptor (VDR) requires identification of structurally distinct areas of VDR-ligand-binding domain (VDR-LBD) important for biological properties of 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)). We hypothesized that covalent attachment of the ligand into VDR-LBD might alter surface structure of that area influencing biological activity of the ligand. We compared anti-proliferative activity of three affinity alkylating derivatives of 1,25(OH)(2)D(3) containing an alkylating probe at 1,3 and 11 positions. These compounds possessed high-affinity binding for VDR; and affinity labeled VDR-LBD. But, only the analog with probe at 3-position significantly altered growth in keratinocytes, compared with 1,25(OH)(2)D(3). Molecular models of these analogs, docked inside VDR-LBD tentatively identified Ser237 (helix-3: 1,25(OH)(2)D(3)-1-BE), Cys288 (beta-hairpin region: 1,25(OH)(2)D(3)-3-BE,) and Tyr295 (helix-6: 1,25(OH)(2)D(3)-11-BE,) as amino acids that are potentially modified by these reagents. Therefore, we conclude that the beta-hairpin region (modified by 1,25(OH)(2)D(3)-3-BE) is most important for growth inhibition by 1,25(OH)(2)D(3), while helices 3 and 6 are less important for such activity.