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PubMedDate not supplied

Autosomal recessive inheritance of congenital goiter in Afrikander cattle.

Congenital goiter was reported in a number of herds of Afrikander cattle in the 1950's. Some affected animals were assembled and maintained as a closed herd. Although considerable biochemical research into the nature of the disease has been conducted, no definitive report has described the mode of inheritance of the defect. This paper presents the results of breeding studies that indicate the defect is inherited as an autosomal recessive. Southern blot analysis of the thyroglobulin gene confirms this finding. In addition, serum levels of TSH (thyroid stimulating hormone, thyrotropin), T3 (3,4,3'-tri-iodothyronine), T4 (thyroxine), rT3 (3,3',5'-tri-iodothyronine), and DIT (diiodotyrosine) of goitrous animals are compared with normal animals.

Africa, Southern↗
PubMedDate not supplied

Inhibition by analogues of L-tyrosine transport by B16/F10 melanoma cells.

The effect of a number of L-tyrosine (L-Tyr) analogues on L-Tyr uptake by B16/F10 malignant melanocytes is reported. This amino acid can be taken up by two of the most ubiquitous transport systems found in animals cells, L and presumably ASC. L-Tyr analogues devoid of the amino group, like p-hydroxyphenyl pyruvic acid and related compounds, and L-Tyr analogues devoid of the carboxyl group, such as tyramine, do not affect L-Tyr uptake. The other aromatic amino acids, L-Phe and L-Trp, and the L-Tyr analogues DL-m-Tyr, L-diiodotyrosine and L-dopa, strongly inhibit the uptake of L-Tyr. This suggests that these chemicals are transported more efficiently than L-Tyr. The ASC system does not show stereospecificity, but the L system has greater affinity for L-Tyr than for D-Tyr. The ASC system also has greater affinity for tyrosine isomers with the hydroxyl group in the ortho and meta positions. The presence of a methyl group at the alpha-carbon of L-Tyr and L-dopa also increases the affinity of the ASC system for these agents. In contrast, alpha-methylation decreases the affinity of the L system in comparison to L-Tyr. Finally, L-Tyr esters do not inhibit, but stimulate the transport of L-Tyr, mainly by the ASC system.

Amino Acid Transport Systems↗
PubMed1977

The thyroidal production of reverse triiodothyronine in autonomous adenoma.

The ratios of reverse triiodothyronine (rT3) to triiodothyronine (T3) concentrations were similar (0.89 +/- 0.09) in twenty-three autonomous thyroid nodules (fourteen decompensated, nine compensated) and paranodular tissues (0.82 +/- 0.08), whereas the serum ratio was significantly lower (0.098 +/- 0.014). This is compatible with the hypothesis that thyroidal rT3 and T3 production from mono- and diiodotyrosine may be a random process in contrast to non-random extrathyroidal rT3 and T3 formation.

Adenoma↗
PubMed1980

Human beta-endorphin: synthesis and characterization of analogs iodinated and tritiated at tyrosine residues 1 and 27.

Three tritiated analogs of human beta-endorphin have been prepared from their corresponding iodinated analogs. The iodinated analogs (diiodotyrosine at positions 1, 27 or 1 and 27) were synthesized by the solid-phase method and were found to have biological and physical properties which were altered when compared with the native molecule. Catalytic exchange of these iodinated analogs in the presence of tritium yielded tritiated human beta-endorphins having full biological activity and specific activity of 50-100 Ci/mmol. Both the iodinated and tritiated beta-endorphin analogs were shown to be homogeneous by chromatography on carboxymethylcellulose, partition chromatography, paper chromatography, amino acid analysis, electrophoresis, high performance liquid chromatography, and isoelectric focusing on polyacrylamide.

Amino Acid Sequence↗
PubMed1982

Protection of methionine in peptides during iodination by sulfonium salt formation.

A method for the prevention of methionine oxidation during iodination of tyrosine containing peptides is reported. The methionine containing peptide is converted into the corresponding S-tert.-butylsulfonium derivative, which is iodinated using iodine monochloride. After removal of the S-tert.-butyl group and purification, sulfoxide-free 3,5 diiodotyrosine (Dit) peptides were obtained. Dit8-substance P, Dit8-physalaemin 6-11 and Dit1, Met5-enkephalin were synthesized by this route. Tritium labeling of Dit1, Met5-enkephalin yielded 3H-enkephalin with a specific radioactivity of 38 Ci/mmol.

Enkephalin, Methionine↗
PubMed1983

Iodogen-catalyzed iodination of transferrin.

Transferrin (human, rabbit) labels at low efficiency (1%-10%) with 125I when reaction of 0.5-0.7 ng of I- (8-10 microCi) with 20 micrograms of the protein is catalyzed by iodogen in a constant volume of 0.1 ml. Microiodination by this technique was therefore analyzed with regard to the relative proportions of the reactants, oxidant requirement, and timing. In vials giving a reaction volume-to-active surface ratio of 0.88, efficiency was independent of the amount of iodogen in the range from 1 microgram to 15 micrograms, and prolongation of the reaction beyond 1 min failed to improve yields. In contrast, the amount of I- present was decisive. Butanol/NH4OH chromatograms of iodination reactions carried out with 0.6 ng or 20 ng of I- showed 3-4 radioactivity peaks, the relative proportions of which markedly depended on the amount of I- present originally. A link was established between labeling efficiency and chromatographic profile of the I- derivatives formed during oxidation. Dual-label experiments in rats showed that transferrin (20 micrograms) can be labeled using iodogen (1-5 micrograms, 1 min) to behave indistinguishably from its IC1-labeled counterpart. However, prolonged exposure to more oxidant progressively damaged the protein. The damage was independent of substituting I and it manifested itself in increased protein binding to the anion exchange resin, Dowex 1-X8. Over 99.5% of the labeled residues in iodotransferrin were mono- and diiodotyrosines (MIT, DIT). DIT content of the protein increased linearly with the number of I atoms substituted. At comparable levels of substitution, more label was present as MIT after using iodogen than after using IC1. Electrophoretic data are presented regarding homogeneity of the label as obtained after iodinating transferrin by different methods and to varying extents.

Animals↗
PubMed1995

Synthesis of alpha-factor analogues containing photoactivatable and labeling groups.

Analogues of alpha-factor, Saccharomyces cerevisiae tridecapeptide mating pheromone (H-Trp-His-Trp-Leu-Gln-Leu-Lys-Pro-Gly-Gln-Pro-Met-Tyr-OH), containing both p-benzoyl phenylalanine (Bpa), a photoactivatable group, and 3-(mono- or di-iodo-4-hydroxyphenyl)propanoic acid (iodinated HPP) or biotin as a tag, were synthesized using solid-phase methodologies on a [phenylacetamido]-methyl (PAM) resin. Bpa was introduced into the peptides using Bpa-hydroxybenzotriazole active ester during peptide chain assembly. Biotinylated alpha-factor analogues were prepared by assembling the desired peptide on the resin, and then reacting a specific amino group either with the symmetrical anhydride of biotin or with biotin using BOP as the activating agent prior to anhydrous hydrogen fluoride cleavage. Iodinated HPP was incorporated by acylating free peptides with Bolton-Hunter reagent (3-[diiodo-4-hydroxyphenyl]propanoic acid hydroxysuccinimide ester) in N,N-dimethylformamide and borate buffer (pH 8.0) solutions. Purification of all peptides to 98% or greater homogeneity was accomplished by high-performance liquid chromatography on a reversed-phase mu-Bondapak C18 column with acetonitrile/water/trifluoroacetic acid as the mobile phase. All products were characterized by amino acid analysis and fast atom bombardment mass spectrometry. Two analogues, alpha-(diiodotyrosine)-His-Bpa-Leu-Gln-Leu-Arg-Pro-Gly-Gln-Pro-Nle-Tyr-O H, and epsilon-(diiodo-HPP)-Lys-His-Bpa-Leu-Gln-Leu-Arg-Pro-Gly-Gln-Pro-Nle-Tyr -OH, were one twentieth to one-fortieth as active as a alpha-factor, and exhibited approximately one order of magnitude lower affinity to the alpha-factor receptor. The results suggest that these two analogues are alpha-factor agonists and that they can be used as probes of the alpha-factor receptor.

Amino Acid Sequence↗
PubMed1980

Purification and characterization of pepsinogens and a unique pepsin from rat stomach.

Four pepsinogens (1, 2, 3 and 4) (zymogens of pepsin A, EC 3.4.23.1, or pepsin C, EC 3.4.23.3) were purified from the fundic mucosa of rat stomach to homogeneous states as judged by sodium dodecyl sulfate/polyacrylamide gel electrophoresis and a unique pepsin was purified from pepsinogen 1. The molecular weights of pepsinogens 1, 2, 3 and 4 were 42 000, 40 000, 40 500 and 39 000, respectively, and those of the respective activated pepsins (1, 2, 3 and 4) were 35 500, 40 000, 35 500 and 37 000, respectively, as estimated by polyacrylamide gel electrophoresis. The amino acid compositions of these four zymogens differed, but resembled those of pepsinogen Cs from various animal species. Rabbit antiserum prepared against pepsinogen 1 reacted with pepsinogen 2, but not with pepsinogens 3 or 4. The precipitin line against pepsinogen 1 fused completely with that against pepsinogen 2. Purified pepsin 1 was a unique pepsin showing remarkable stability in alkali. It resembled pepsin A with respect to inhibition by pepstatin and pepsin C with respect to its amino acid composition, but had properties intermediate between those of pepsin A and C with respect to its optimal pH (2.1 to 3.1) with hemoglobin and activity on N-acetyl-L-phenylalanyl-L-diiodotyrosine.

Amino Acids↗
PubMed1984

Evidence for the glycoprotein nature of retina glycogen.

Incubation of a bovine retina membrane preparation with micromolar amounts of UDP-[14C]glucose resulted in the incorporation of [14C]glucose into endogenous (1----4)-alpha-glucan, insoluble in trichloroacetic acid, and acid-soluble ethanol-insoluble glycogen. The trichloroacetic-acid-insoluble glucan fraction of retina migrated in 2.6-3% acrylamide gels when subjected to sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE) and was rendered acid-soluble by digestion with pronase. The solubility of the acid-insoluble glucan in acidified organic solvent was different from that of amylose or glycogen and similar to membrane proteins and glycoproteins. The glycogen fraction of retina contained 1.5-2.0 micrograms protein/100 micrograms glucose. When this fraction was analyzed by SDS-PAGE only one band, which moved near the top of 3% acrylamide gels, was stained with periodic acid Schiff reagent and Coomassie blue. The protein nature of the Coomassie-blue-stainable material was demonstrated by iodination of the glycogen fraction with [131I]iodide and identification of labeled monoiodotyrosine and diiodotyrosine. The bulk of the label comigrated with carbohydrate near the top of gels in SDS-PAGE and treatment with alpha- amylse decreased the molecular size of both labeled and stainable material. Physical dissociative conditions (7.5 M urea/0.83% SDS/0.83% mercaptoethanol) and the following chemical treatments failed to dissociate the iodinated protein from glycogen: (a) 0.1 M NaOH/0.1 M NaBH4 at room temperature for 24 h; (b) 1 M HCl in methanol at 50 degrees C for 10 min; (c) trifluoroacetic acid at 50 degrees C for 6 min. 131I-labeled glycogenpeptide was isolated after 131I-labeled protein-bound glycogen had been subjected to digestion with papain/pronase and passed through a Sepharose column. The results suggest that at least part of glycogen in bovine retina is firmly combined to protein as a single proteoglycogen molecule. Furthermore some of the proteoglycogen might be present as a trichloroacetic-acid-precipitable proteoglucan owing to its lower glucose content.

Animals↗
PubMed1986

Structural differences around hormonogenic sites on thyroglobulins from different species detected by monoclonal antibodies.

Thyroxine remains attached to its synthetic site in thyroglobulin until it is released by proteolysis. Strong homology in the primary sequence surrounding thyroxine-forming residues in thyroglobulins from various species suggests a unique three-dimensional structure at hormonogenic sites. To examine this, two thyroxine-binding mouse anti-(chicken thyroglobulin) monoclonal antibodies, 1A10 and 5F6, were used as probes for this region in an enzyme-linked immunosorbent inhibition assay. The thyroxine content of thyroglobulins had a marked positive influence on the monoclonal antibody binding: when the thyroxine content of human thyroglobulin rose by 6.6-fold, cross-reactivities rose 25-fold for the 1A10 monoclonal antibody and 17.6-fold for the 5F6 monoclonal antibody. However, interspecies comparison of thyroglobulin preparations with similar thyroxine content showed lower than expected cross-reactivities for human, pig and sheep thyroglobulins when compared with chicken thyroglobulin. Only when the thyroxine content of heterologous thyroglobulin preparations was two or three times higher did the cross-reactivities equal or surpass that of chicken thyroglobulin. It is concluded that in thyroglobulin there are structural differences in the different animal species near the thyroxine-forming sites bound by these monoclonal antibodies. The known primary sequence similarity does not seem to result, therefore, in identical three-dimensional structures about this site. These differences may reflect species-specific variations in distant regions brought close as a result of chain folding to form the hormonogenic site, such as those around the donor diiodotyrosine residue or in polysaccharide structures. These monoclonal antibodies provide information about the structure of thyroglobulin, which cannot be obtained from knowledge of the amino acid sequence alone.

Animals↗
PubMed1988

Tuna pepsinogens and pepsins. Purification, characterization and amino-terminal sequences.

Three pepsinogens (pepsinogens 1, 2, and 3) were purified from the gastric mucosa of the North Pacific bluefin tuna (Thunnus thynuus orientalis). Their molecular masses were determined to be 40.4 kDa, 37.8 kDa, and 40.1 kDa, respectively, by SDS/polyacrylamide gel electrophoresis. They contained relatively large numbers of basic residues when compared with mammalian pepsinogens. Upon activation at pH 2.0, pepsinogens 1 and 2 were converted to the corresponding pepsins, in a stepwise manner through intermediate forms, whereas pepsinogen 3 was converted to pepsin 3 directly. The optimal pH of each pepsin for hemoglobin digestion was around 2.5. N-acetyl-L-phenylalanyl-L-diiodotyrosine was scarcely hydrolyzed be each pepsin. Pepstatin, diazoacetyl-DL-norleucine methyl ester in the presence of Cu2+, 1,2-epoxy-3-(p-nitrophenoxy)propane and p-bromophenacyl bromide inhibited each pepsin, although the extent of inhibition by each reagent differed significantly among the three pepsins. The amino acid sequences of the activation segments of these pepsinogens were determined together with the sequences of the NH2-terminal regions of pepsins. Similarities in the activation segment region among the three tuna pepsinogens were rather low, ranging over 28-56%. A phylogenetic tree for 16 aspartic proteinase zymogens including the three tuna pepsinogens was constructed based on the amino acid sequences of their activation segments. The tree indicates that each tuna pepsinogen diverged from a common ancestor of pepsinogens A and C and prochymosin in the early period of pepsinogen evolution.

Amino Acid Sequence↗
PubMed1973

Pentapeptide (pepstatin) inhibition of brain acid proteinase.

The pentapeptide pepstatin obtained from culture filtrates of actinomycetes completely inhibited brain acid proteinase (cathepsin D) at exceedingly low concentrations. Among the brain enzymes tested, the effect is specific for acid proteinase because addition of 1000-fold higher concentrations was without effect on neutral proteinase, aminopeptidase, and arylamidases. Pepstatin also inhibits pepsin as tested with hemoglobin or with N-acetylphenylalanyl-L-diiodotyrosine as substrate. Pepstatin must be regarded as the most powerful agent yet described that inhibits intracellular acidic proteolytic enzyme in brain.

Actinomyces↗
PubMed1985

The renal handling of human urinary ribonuclease by rat kidneys.

The purpose of the study was to find out how poly(C)-avid human urinary ribonuclease is handled by the kidney. Purified human urinary ribonuclease (molecular weight 33 000) was radiolabelled with 125I. The enzyme was injected intravenously into dogs and monkeys with and without kidneys. The disappearance rate from the animals without kidneys was markedly prolonged. In the dog and monkey with kidneys, the radiolabelled enzyme which was infused was recovered in the urine unchanged. No large molecular weight fragments were found. When 125I-labelled ribonuclease was infused into rats the material recovered in the urine was primarily identical with the material infused. A very small fraction of the material recovered was found to contain some fragments which had chromatographic characteristics of monoiodotyrosine and diiodotyrosine. Two other fragments were detected but could not be identified. Autoradiographic studies of the rat kidneys also showed some reabsorption of the radiolabelled ribonuclease, particularly in the proximal tubules. With electron microscopy the radiolabelled material could be seen in the lysosomes. These observations corroborate findings discovered for other low molecular enzyme such as lysozyme (molecular weight 14 000) and suggest that the human ribonuclease is mainly excreted by the kidneys unchanged and that a minor amount may be reabsorbed by the proximal tubules and metabolized in the lysosomes.

Animals↗
PubMed1976

The pepsinogens of cat gastric mucosa and the pepsins derived from them.

Fundic mucosal extracts of the cat were examined by chromatography using DEAE-cellulose at pH 5.3. The peaks of proteolytic activity located by this method were shown to be heterogeneous on electrophoresis. By electrophoresis of individual homogenous chromatographic fractions 9 separate zones of proteolytic activity were detected. One zone did not migrate from the origin and is possibly a non-pepsinogen gastric protease. Simultaneous electrophoresis of pepsinogens and pepsins indicated that each pepsinogen gave rise to one pepsin. One zymogen gives rise to a pepsin active with the synthetic substrate acetyl-L-phenylalanyl-L-diiodotyrosine (APDT).

Animals↗
PubMed1969

Myocardial adenyl cyclase: activation by thyroid hormones and evidence for two adenyl cyclase systems.

The mechanism responsible for the hyperdynamic circulatory state in hyperthyroidism has not been defined. Although certain cardiac manifestations resemble those caused by excessive adrenergic stimulation, recent evidence suggests that thyroid hormone exerts an effect on the heart that is independent of the adrenergic system. Since the inotropic and chronotropic effects of norepinephrine appear to be mediated by activation of adenyl cyclase, the possibility that thyroxine and triiodothyronine are also capable of activating adenyl cyclase was examined in the particulate fraction of cat heart homogenates.L-thyroxine and L-triiodothyronine increased the conversion of adenosine triphosphate-(32)P (ATP-(32)P) to cyclic 3',5'-adenosine monophosphate-(32)P (3',5'-AMP-(32)P) by 60 and 45% respectively (P < 0.01). A variety of compounds structurally related to the thyroid hormones, but devoid of thyromimetic activity did not activate adenyl cyclase: these included 3,5-diiodo-L-thyronine, L-thyronine, 3,5-diiodotyrosine, monoiodotyrosine, and tyrosine. D-thyroxine activated adenyl cyclase and half maximal activity was identical to that of the L-isomer. Although the beta adrenergic blocking agent propranolol abolished norepinephrine-induced activation of adenyl cyclase, it failed to alter activation caused by thyroxine. When maximal concentrations of L-thyroxine (5 x 10(-6) moles/liter) and norepinephrine (5 x 10(-5) moles/liter) were incubated together, an additive effect on cyclic 3',5'-AMP production resulted. THIS INVESTIGATION DEMONSTRATES: (a) thyroid hormone is capable of activating myocardial adenyl cyclase in vitro and (b) this effect is not mediated by the beta adrenergic receptor. Moreover, the additive effects of norepinephrine and thyroxine suggest that at least two separate adenyl cyclase systems are present in the heart, one responsive to norepinephrine, the other to thyroid hormone. These findings are compatible with the hypothesis that the cardiac manifestations of the hyperthyroid state may, in part, be caused by the direct activation of myocardial adenyl cyclase by thyroid hormone.

Adenine Nucleotides↗
PubMed1973

Radioimmunoassay for measurement of thyroglobulin in human serum.

A specific and reproducible double antibody radioimmunoassay for the measurement of thyroglobulin (HTg) in human serum has been developed. Since antithyroglobulin autoantibodies combine with the [(131)I] HTg tracer, antibody-positive sera were rejected for measurement. Specificity is demonstrated in that thyroid analogous such as thyroxine (T(4)), triiodothyronine (T(2)) monoiodotyrosine (MIT) and diiodotyrosine (DIT) did not crossreact. Sera previously reacted with anti-HTg-Sepharose contained no immunoassayable HTg. Finally, sera obtained from patients after total thyroid ablation for thyroid carcinoma did not contain demonstrable HTg. The sensitivity of the assay is 1.6 ng/ml, and HTg was detectable in 74% of 95 normal subjects. The mean concentration was 5.1 ng/ml +/-0.49 SEM (range <1.6-20.7 ng/ml). Day to day variation in HTg levels is large in some euthyroid subjects and nearly absent in others. HTg was detectable in 90% of the sera obtained in 23 pregnant women at delivery in whom a mean concentration of 10.1 ng/ml +/-1.3 SEM was observed. The mean level for the corresponding newborn infants at birth was 29.3 ng/ml +/-4.7 SEM a value significantly higher than the mean maternal HTg concentration (P <0.01). A group of 17 thyrotoxic individuals all had elevated HTg levels; the mean for this group was 344.8 ng/ml +/-90.7 SEM. In the acute phase of subacute thyroiditis HTg was also elevated in all of 12 patients, and the mean for this group was 136.8 ng/ml +/-74.6 SEM.

Adolescent↗
PubMed1975

A radioimmunoassay for serum rat thyroglobulin. Physiologic and pharmacological studies.

A double antibody radioimmunoassay has been developed to measure thyroglobulin in rat (RTg) serum. The lowest detectable quantity measurable was 5.0 ng/ml. Specificity was documented by: (a) fall in serum RTg to undetectable levels after thyroid ablation; (b) the fact that L-thyroxine, D-thyroxine, L-triiodothyronine, D-triiodothyronine, triiodothyroacetic acid, tetraiodothyroacetic acid, triiodothyropropionic acid, moniodotyrosine, diiodotyrosine, and human thyroglobulin (HTg) in concentrations up to 40,000 ng per tube did not cross-react in the assay; (c) the demonstration that constant levels of serum RTg were observed while varying amounts of serum (criterion of parallelism) were introduced in the assay. The mean RTg concentration in tail vein blood of adult Sprague-Dawley rats were 101.5 +/- 13.0 ng/ml (SEM) (n=21); values ranged from 12.0 to 258.0 ng/ml. Chronic administration of a high-iodine diet (HID) did not affect serum thyroglobulin levels. Chronic administration of a low-iodine diet (LID) and propylthiouracil (PTU) led to a statistically significant increase in serum RTg that was accompanied by a significant rise in serum thyrotropin (rTSH). Serum thyroxine (T4) administered to normal rats for 14 days (20 mug/day subcutaneously) depressed serum RTg concentration from a mean level of 119.4 +/- 17.5 ng/ml (n=19) to a mean of 35.0 +/- 0.27 ng/ml (n=19) (P less than 0.001). While rats were on continuous T4 suppression, bovine thyroid-stimulating hormone (bTSH) given intravenously (2 IU) resulted in a mean maximal increment of RTg of 332.0 +/- 81.5 ng/ml (n=6) at 24 h. IgC-(LATS) long-acting thyroid stimulatory injected intravenously resulted in a mean maximal increment of RTg concentration at 96 h of 87.2 +/- 14.3 ng/ml (n=5). Normal IgG had no statistical significant effect of RTg levels at any time after the injection.

Animals↗
PubMed1976

Altered thyroidal responsivity to thyrotropin induced by circulating thyroid hormones. A "short-loop" regulatory mechanism?

We studied the effect of thyroid hormone administration on responsivity of murine thyroid to exogenous thyrotropin (TSH) in order to explore the possibility that the thyroid gland might be directly inhibited by its own hormones. In the rat both L-thyroxine (T4) and 3,5,3'-L-triiodothyronine (T3) pretreatment inhibited TSH-induced thyroidal ornithine decarboxylase (ODC) activity in vivo in a dose-related manner (half-maximal inhibition, 1.7 mug/rat and 0.6 mug/rat, respectively). Other structurally related compounds exhibited the following inhibitory potencies compared to T4: T3, 283%; triiodothyroacetic acid, 40%; D-T4, 18%; 3,5-L-diiodothyronine, 9%. Monoiodotyrosine, diiodotyrosine, and iodide were not inhibitory. The full inhibitory effect of T4 or T3 was observed when thyroid hormone was administered from 96 to 12 h before TSH and was also seen in hypophysectomized animals. Pretreatment with T4 or T3 in divided doses over 2 1/2 days inhibited TSH-induced increase in [1-14C]glucose oxidation to 14C02 and [3H] leucine incorporation into protein in rat thyroid. In the mouse T4 or T3 pretreatment (0.25-25 mug daily) caused dose-related inhibition of both thyroidal ODC activity and 131I release induced by TSH in vivo. In mice on a low-iodine diet (LID) but not in animals on a regular diet (RD) NaI pretreatment also blunted TSH-induced thyroidal ODC activation and 131I release. When LID or RD mice were pretreated with 12.5-125 mug of T4 or T3 over 2 1/2 days, TSH-induced in vitro stimulation of thyroid cyclic 3',5'-adenosine monophosphate formation was inhibited in a dose-related manner; NaI pretreatment was inhibitory in the LID mouse only. Prior administration of exogenous TSH blunted the activation of thyroid ODC and thyroid hormone release induced by subsequent TSH administration in rat and mouse. These studies indicate altered thyroid responsivity to TSH under the influence of circulating thyroid hormones and suggest the existence of a "short-loop" negative feedback regulating thyroid function.

Animals↗