Detail of "5817-39-0"

Reference

Partial purification of the triiodothyronine receptor from rat liver nuclei

Partial purification of the triiodothyronine receptor from rat liver nuclei. Differences in the chromatographic mobility of occupied and unoccupied sites. Silva, Enrique S.; Astier, Helene; Thakare, Usha; Schwartz, Harold L.; Oppenheimer, Jack H. (Dep. Med., Univ. Minnesota, Minneapolis, Minn., USA). J. Biol. Chem., 252(19), 6799-805 (English) 1977. CODEN: JBCHA3. DOCUMENT TYPE: Journal CA Section: 2 (Hormone Pharmacology) Section cross-reference(s): 9 A 60-125-fold purifn. of nuclear exts. from rat liver triiodothyronine (I) [6893-02-3] receptor was achieved by dialysis of 0.4M NaCl nuclear exts. followed by chromatog. on DEAE-Sephadex. The ext. was labeled either by injecting tracer I-125I into the animal or by direct addn. of the tracer in vitro prior to chromatog. Elution of the column with a linear NaCl gradient revealed a single peak of specific binding activity at 0.15M NaCl and Scatchard plots of the solubilized receptors showed a single binding component with an apparent Kd of .apprx.2.0 .times. 10-10M. The relative binding affinities of the solubilized receptors for I, thyroxine [51-48-9], 3,5',3'-triiodothyronine [5817-39-0], and 3'-isopropyl-3,5-diiodothyronine [51-23-0] were similar to thosepreviously obsd. in whole nuclei. By incubating nuclear exts. from euthyroid animals at 0.degree., which minimizes dissocn. of I, and at 30.degree., which facilitates such dissocn. it was possible to show that .apprx.40% of the receptor sites were occupied. The binding capacity of exts. from hypothroid animals was similar to that from euthyroid animals. Binding of I to the nuclear receptor altered the chromatog. mobility of the receptor. Occupied sites labeled with tracer I prior to DEAE-Sephadex chromatog. eluted at 0.15M NaCl. Unoccupied sites labeled at 0.degree. after chromatog. sepn. showed a peak of specific binding activity at 0.18M NaCl. Addn. of tracer to previously unlabeled chromatog. eluates which were subsequently warmed to 30.degree. for 40 min in order to allow exchange with the endogenous I revealed 2 peaks of binding activity, at 0.15 and at 0.18M NaCl. These were presumed to represent the occupied and unoccupied sites, resp. Even though no differences between the sedimentation characteristics of occupied and unoccupied sites was detected, the shift in chromatog. mobility is compatible with a ligand-induced alteration in receptor conformation. This may be of importance as a step in the initiation of hormonal action.

Interference of dimethyl a-(dimethoxyphosphinyl)-p-chlorobenzylphosphate (SR-202) in thyroid hormone metabolism: evidence of inhibition of monodeiodination

Interference of dimethyl a-(dimethoxyphosphinyl)-p-chlorobenzylphosphate (SR-202) in thyroid hormone metabolism: evidence of inhibition of monodeiodination. Liniger, C.; Pometta, D.; Burger, A. G. (Dep. Med., Univ. Geneva, Geneva 1211, Switz.). J. Endocrinol., 112(1), 171-5 (English) 1987. CODEN: JOENAK. ISSN: 0022-0795. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 2 SR-202 [76541-72-5] is a noniodinated, potential lipid-altering agent. When administered 300 mg/day for 3 days) to euthyroid subjects it caused a 30% fall in a reciprocal 104% rise in 3,3',5'-triiodothyronine (rT3) [5817-39-0] and a 37% rise in thyroxine (T4) [51-48-9]. Basal and TRH-stimulated TSH [9002-71-5] did not change. These results suggest that SR-202 acts as an inhibitor of the peripheral monodeiodination of T4 to T3. During a 2nd study the same subjects received the same dose of SR-202 for a further 3 days following block of TSH, T4, T3, and rT3 secretion with L-T4. Despite higher levels of thyroid hormones in those subjects than before, similar results were obsd. with SR-202, serum T3 falling by 40% and serum rT3 and T4 rising by 168 and 37%, resp. These changes provide evidence that SR-202 is an inhibitor of the peripheral conversion of T4 to T3 and acts on thyroid hormone metab. without provoking a counter-regulatory pituitary response. It might be a useful tool for the clin. investigation of thyroid function.