Reference

Metabolism of thyroid hormones by cultured monkey hepatocarcinoma cells

Metabolism of thyroid hormones by cultured monkey hepatocarcinoma cells. Nonphenolic ring deiodination and sulfation. Sorimachi, Kenji; Robbins, Jacob (Natl. Inst. Arthritis, Metab. Dig. Dis. 64192-58-1 is just another one chemical used in this study., NIH, Bethesda, Md., USA). J. Biol. Chem., 252(13), 4458-63 (English) 1977. CODEN: JBCHA3. DOCUMENT TYPE: Journal CA Section: 2 (Hormone Pharmacology) The metab. of 3,5,3'-L-triiodothyronine (I) [6893-02-3] and L-thyroxine (II) [51-48-9] was investigated in cultured hepatocytes (NCLP-6E) derived from a rhesus monkey hepatocarcinoma. Hormones labeled with 125I in the phenolic ring were added to the medium of cell monolayers. After I addn., the concn. of 125I in the medium fell to .apprx.50% of the starting level within 30 min. At 37.degree., but not at 4.degree., this was followed by a rise to .apprx.90% within 5 h. Chromatog. anal. showed almost complete disappearance of I, and the sequential appearance of 3,3'-L-diiodothyronine (T2) [4604-41-5], 3'-L-monoiodothyronine (T1) [4732-82-5], and a component which was shown by sulfatase treatment to be the phenolic sulfate conjugates of T2 and T1. The T2 sulfoconjugate accounted for .apprx.85% of the 125I in the medium after 7 h. At 4.degree., no metabolites of I were obsd. II was also metabolized by the cells at 37.degree. but not at 4.degree., although the rate was much slower. The major metabolite was 3,3'5'-L-triiodothyronine (rT3) [5817-39-0]. After 18 h, .apprx.40% of the 125I in the medium was unaltered II, and .apprx.20 and .apprx.15% were rT3 and 3,3'-L-diiodothyronine sulfate [64192-57-0], resp. Labeled I was not detected in the medium and accounted for no more than .apprx.1.5% of the intracellular radioactivity. After incubation of cells with 125I-labeled rT3 for 24 h, 28% of the medium 125I was T2 sulfate, indicating that the major pathway for T2 and I- prodn. from II was via rT3 deiodination. The metab. of I and II was saturable, and was partially inhibited by either I or II at .apprx.10-8M, and completely inhibited at .apprx.10-6M. The NCLP-6E hepatocarcinoma cells are apparently very active in carrying out nonphenolic ring deiodination of the thyroid hormones, as well as sulfoconjugation of the partially deiodinated products. .

Effects of small doses of bovine TSH on serum levels of free and total thyroid hormones, their degradation products, and diiodotyrosine

Effects of small doses of bovine TSH on serum levels of free and total thyroid hormones, their degradation products, and diiodotyrosine. Benker, G.; Splittstoesser, C.; Meinhold, H.; Olbricht, T.; Reinwein, D. (Med. Klin. Poliklin., Univ. Essen, Essen, Fed. Rep. Ger.). Acta Endocrinol. (Copenhagen), 108(2), 211-16 (English) 1985. CODEN: ACENA7. ISSN: 0001-5598. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) Bovine TSH [9002-71-5] was administered i.v. to normal volunteers in doses of 2.5-30 milliunits/kg. Brisk elevations of serum diiodotyrosine [300-39-0] occurred after the smallest dose (mean, +183%), whereas larger doses had only slight addnl. effects. T3 [6893-02-3] rose much higher than T4 [51-48-9] (+71% compared with +23% after 15 milliunits TSH/kg), and free (f) thyroid hormones exhibited changes similar to total T3 and total T4. The mean abs. increase in serum fT3 was 2.03-9.04 pmol/L and was an easily measurable parameter for the TSH effect. Dose-response effects were seen for the increases of fT4, fT3, and T3. T4-binding globulin and rT3 did not change, but the degrdn. product 3,3'-diiodothyronine [4604-41-5] showed large increments of serum levels. There was no correlation between the responses of T3 and T4, of fT3 and fT4, or of diodotyrosine and any of the other parameters of thyroid function. The interindividual differences in the magnitude of thyroid hormone response to TSH were considerable, and there was no relation between this response and thyroid vol. by ultrasound. Thus, direct stimulation of the thyroid gland with TSH in small doses leads to consistent increases of thyroid hormones, esp. T3 and fT3, and the precursor diiodotyrosine is released together with thyroid hormones. However, the response varies between individuals.