Action of Topical Thyroid Hormone Analogue, Triiodothyroacetic Acid in Reversing Glucocorticoid-Induced Skin Atrophy in Humans

Thyroid ◽  
2006 ◽  
Vol 16 (11) ◽  
pp. 1157-1162 ◽  
Author(s):  
Parviz Yazdanparast ◽  
Bo Carlsson ◽  
Aarne Oikarinen ◽  
Juha Risteli ◽  
Thomas Lavin ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Skin Atrophy ◽  
Hormone Analogue

A Thyroid Hormone Analogue, Triiodothyroacetic Acid, Corrects Corticosteroid-Downregulated Collagen Synthesis

Thyroid ◽  
2004 ◽  
Vol 14 (5) ◽  
pp. 345-353 ◽  
Author(s):  
Parviz Yazdanparast ◽  
Bo Carlsson ◽  
Aarne Oikarinen ◽  
Juha Risteli ◽  
Jan Faergemann
Keyword(s):  
Thyroid Hormone ◽  
Collagen Synthesis ◽  
Hormone Analogue

Action of Topical Thyroid Hormone Analogues on Glucocorticoid-Induced Skin Atrophy in Mice

Thyroid ◽  
2006 ◽  
Vol 16 (3) ◽  
pp. 273-280 ◽  
Author(s):  
Parviz Yazdanparast ◽  
Bo Carlsson ◽  
Xing-Ying Sun ◽  
Xiao-He Zhao ◽  
Thomas Hedner ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Skin Atrophy

Use of the Thyroid Hormone Analogue Eprotirome in Statin-Treated Dyslipidemia

2010 ◽  
Vol 65 (8) ◽  
pp. 512-513
Author(s):  
Paul W. Ladenson ◽  
Jens D. Kristensen ◽  
E. Chester Ridgway ◽  
Anders G. Olsson ◽  
Bo Carlsson ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Hormone Analogue

Clinical and Experimental Studies on the Use of 3,5-Diiodothyropropionic Acid, a Thyroid Hormone Analogue, in Heart Failure

Thyroid ◽  
2002 ◽  
Vol 12 (6) ◽  
pp. 527-533 ◽  
Author(s):  
Eugene Morkin ◽  
Gregory D. Pennock ◽  
Peter H. Spooner ◽  
Joseph J. Bahl ◽  
Steven Goldman
Keyword(s):  
Heart Failure ◽  
Thyroid Hormone ◽  
Experimental Studies ◽  
Hormone Analogue

The thyroid hormone analogue SKF L-94901: nuclear occupancy and serum binding studies

1989 ◽  
Vol 76 (5) ◽  
pp. 495-501 ◽  
Author(s):  
John W. Barlow ◽  
Lorna E. Raggatt ◽  
Chen-Fee Lim ◽  
Sharon L. Munro ◽  
Duncan J. Topliss ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Serum Proteins ◽  
Binding Studies ◽  
Hormone Analogue ◽  
Isolated Nuclei ◽  
Whole Cells ◽  
High Affinity ◽  
Nuclear Extracts

1. We studied a brominated thyroid hormone analogue, SKF L-94901, which has the potential to lower serum cholesterol without adverse cardiovascular effects. This compound is about 50% as active as tri-iodothyronine (T3) in liver nuclear receptor binding in vivo but only 1% as active in vitro and has nearly 200 times more enzyme-inducing activity in liver than in heart. Our aim was to examine the interaction of SKF L-94901 with [125I]T3 binding to the intact nuclei in whole cells, isolated nuclei and nuclear extracts of human HeLa cells and to investigate the binding of this compound to human serum. 2. Relative to thyroxine (T4), the affinity of this compound for T4-binding globulin was 0.0035%, for transthyretin 1.66% and for albumin 1.26%. Low affinity for serum proteins, with a relatively high circulating free fraction, could explain why SKF L-94901 is more potent in vivo than in vitro. 3. Human HeLa cell nuclei, isolated after whole-cell incubations, bound [125I]T3 with high affinity (Kd = 78 ± 8 pmol/l, mean ± sem), which was displaceable by T3 analogues in the order Triac {[4-(4-hydroxy-3-iodophenoxy)-3,5-di-iodophenyl]acetic acid} > T3 > T4 ≫ reverse T3. Similar high-affinity (Kd = 58 ± 6 pmol/l, mean ± sem) and identical specificity was observed in high-salt (0.4 mol/l KCl) nuclear extracts. In nuclei of whole cells incubated with [125I]T3 and SKF L-94901, the analogue was 0.8% as potent as T3, whereas in experiments with nuclear extract, the analogue was 7.7% as potent as T3. Results from incubation of T3 with isolated nuclei were virtually identical to those obtained with nuclear extracts. 4. These results suggest an extranuclear component may be involved in restricting access of SKF L-94901 to the nucleus. Whether such mechanisms account for observed differences in its effects on different tissues with reduced influence of SKF L-94901 on cardiac tissue remains to be established. 5. We conclude that SKF L-94901 is weakly bound in serum and shows less potent competition for T3 nuclear binding after incubation of whole cells than after incubation with nuclear extracts or isolated nuclei. This compound may allow further analysis of intracellular mechanisms of thyroid hormone transport and action.

scholarly journals Chemically-Modified Tetraiodothyroacetic Acid (Tetrac) Induces Cancer Cell Apoptosis and Facilitates Clearance of Apoptotic Debris (Efferocytosis)

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A1012-A1013
Author(s):  
Kavitha Godugu ◽  
Hung-yun Lin ◽  
Shaker A Mousa ◽  
Paul J Davis
Keyword(s):  
Thyroid Hormone ◽  
Drug Treatment ◽  
Tumor Cell ◽  
Molecular Mechanisms ◽  
Integrin Αvβ3 ◽  
Hormone Analogue ◽  
Human Glioblastoma ◽  
Chemically Modified ◽  
End Of Treatment ◽  
Apoptotic Change

Abstract Tetraiodothyroaetic acid (tetrac) is a derivative of L-thyroxine with anticancer properties. By multiple molecular mechanisms, tetrac and chemically-modified tetrac induce apoptosis in a variety of human cancer cells in vitro and in xenografts. The anticancer activities of tetrac are initiated at the thyroid hormone analogue receptor on the extracellular domain of plasma membrane integrin αvβ3 (PJ Davis et al., Physiol Rev 101:319-352, 2021). Induction of apoptosis in glioblastoma xenograft with chemically modified tetrac (P-bi-TAT) has yielded 90% in volume of grafts that continues after discontinuation of tetrac. In the present study, we show that human glioblastoma xenograft shrinkage in response to P-bi-TAT is associated with local appearance of phagocytic monocytes and clearance of apoptotic debris (efferocytosis). Primary culture xenograft of glioblastoma cells (GBM 052814, kindly provided by the University of Pittsburgh Medical Center, Department of Neurosurgery) and U87-luc (ATCC, Manassas, VA) xenografts were generated in 5-member groups of nude mice for each tumor cell type and for controls. Five days post-implantation, injection of animals was begun with PBS (control) or P-bi-TAT (10 mg/kg body weight). Injection was continued X21 days and animals were then maintained off-treatment for an additional 21 days. Tumors were harvested, formalin-fixed and slide-mounted, then analyzed by TUNEL assay for apoptosis and by anti-CD68 staining for monocytic macrophage content. Histologic analysis (H&E staining) was also carried out. TUNEL analysis and histopathology of both xenograft models revealed more than 90% apoptotic change with 21-days of P-bi-TAT treatment (P <0.001) and persistence of 40% apoptotic change 3 weeks post-discontinuation of drug (P<0.001 vs. end of treatment change). By H&E histology and CD68 analysis, monocytes accounted for more than 90% of the viable cells after 3 weeks’ drug treatment. Sixty percent of the end-of-treatment monocyte population persisted 3 weeks after discontinuation of P-bi-TAT (P <0.001). Histology revealed negligible cell debris after 3 weeks of drug treatment and at 3 weeks post-discontinuation of P-bi-TAT. Thus, the anticancer/pro-apoptotic action of tetrac-containing P-bi-TAT is associated with efferocytosis that contributes to the frank tumor shrinkage that results from P-bi-TAT treatment of human glioblastoma xenografts. This is the first documentation of efferocytosis regulated from the thyroid hormone analogue receptor on tumor cell integrin αvβ3.

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