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Biomedical subjects

V A Galton

Publications and source records attributed to V A Galton.

At least 19 recordsLinked to original sources
PubMed1992

Thyroid hormone receptors and iodothyronine deiodinases in the developing Mexican axolotl, Ambystoma mexicanum.

The Mexican axolotl, Ambystoma mexicanum, is a neotenous salamander that rarely undergoes anatomical metamorphosis, but can be induced to do so by administration of thyroxine (T4). The neoteny appears to be due primarily to low levels of plasma T4 secondary to a low rate of secretion of thyroid-stimulating hormone. However, other factors may also be involved. In anuran amphibia, metamorphosis is accompanied by alterations in thyroid hormone receptor concentration and marked changes in the activities of the iodothyronine deiodinase systems, all of which contribute to enhancing peripheral sensitivity to circulating T4. The present study was designed to assess these functions in the tissues of the axolotl. Putative 3,5,3'-triiodothyronine (T3) receptors were readily detected in axolotl red blood cells, and the receptor number (sites/nucleus) showed a developmental decline, comparable to that seen in anuran amphibia, as the larval cells with a high receptor number were replaced with adult cells with a low receptor number. Saturable T3 nuclear binding sites were also detected in liver, but the receptor number was too low to quantitate. Using a sensitive RIA, T4 and T3 were below detectable levels in juvenile axolotls and T4 was just detectable in some of the adults. Following injection of [125I]T4, [125I]T3 was detected in plasma and liver of adult, but not of juvenile, axolotls. Some 5'-deiodinase activity was consistently detected in preparations of larval skin, and in adult skin and gut, but it was too low to permit kinetic analyses. Activity was not increased following treatment with sufficient T4 to induce anatomical metamorphosis. 5-Deiodinase activity was not detected in any tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1991

The ontogeny of iodothyronine deiodinase systems in liver and intestine of the rat.

The ontogeny of the iodothyronine deiodinase systems has been studied by several investigators in recent years, but our understanding of the subject is far from complete. The present study was conducted to obtain kinetic information concerning 5' deiodinase (5'D) and 5 deiodinase (5D) activities in fetal rat liver and intestine, and to examine reduced glutathione (GSH)-activated 5'D activity in the two tissues. When dithiothreitol (DTT) was used as cofactor in concentrations up to 100 mM, 5'D activity was not clearly detected in liver or intestine until day 16 of gestation. Activity increased markedly in both tissues between fetal day 18-21, due primarily to an increase in maximum velocity (Vmax) of the enzyme. However, whereas 5'D activity was much higher in adult liver than in fetal liver [due to both an increase in Vmax and a decrease in the Michaelis-Menten constant (Km)], activity was barely detectable in adult intestine. When GSH was used as cofactor, the temporal development of activity in both tissues was comparable to that observed with DTT, but kinetic values were very different; with DTT mean values for Vmax in liver ranged from 3.7-1264 pmol I-/h.mg protein, and values for Km ranged from 0.1-0.5 microM; with GSH, values for Vmax ranged from 0.4-16.7 pmol I-/h.mg protein, and values for Km were less than 1 nM. A comparable difference was observed also in intestine. When either DTT or GSH was used as cofactor, 5'D activity was inhibited in the presence of 6n-propyl-2-thiouracil or iopanoic acid. Using T3 as substrate it was found that 5D activity was much higher in intestine than in liver, and the amount of 5D activity in intestine paralleled that in brain in that it was much higher in fetal than in adult tissue. Moreover, values for Vmax and Km in fetal intestine were comparable to those in fetal brain. These findings suggest that thyroid hormone is important in the developing rat intestine and raise the possibility that GSH could be the activator of 5'D systems in vivo.

Aging↗
PubMed1991

The role of thyroid hormone in the regulation of hepatic carbamyl phosphate synthetase activity in Rana catesbeiana.

Both spontaneous and thyroid hormone (TH)-induced metamorphosis of Rana catesbeiana are accompanied by a marked increase in the activity of the urea cycle enzyme carbamyl phosphate synthetase (CPS). The increase induced by exogenous TH is de novo synthesis of enzyme and appears to be secondary to an increase in the CPS mRNA level resulting from the elevated plasma TH. Since endogenous TH levels rise sharply during spontaneous metamorphosis, a similar sequence of events would be anticipated. However, after midclimax, CPS activity continues to increase, while plasma TH levels steadily decline, suggesting that other factors are involved. To obtain insight into this problem, the changes in CPS mRNA level during spontaneous development were determined using a mammalian CPS cDNA probe and correlated with changes in CPS activity and plasma T3 concentration. CPS mRNA level and CPS activity were barely detectable until midprometamorphosis, but both increased rapidly during the latter half of this phase. CPS activity continued to rise, reaching a maximum in the adult frog. The CPS mRNA level, however, was highest during the first half of climax, but declined after midclimax and was relatively low in the adult frog. Studies were also performed in which the rise and fall in the plasma T3 concentration typical of metamorphic climax were induced by exposure of premetamorphic tadpoles to T3, followed by its withdrawal. Both CPS activity and CPS mRNA level were induced by T3, but when plasma T3 levels fell after removal of the exogenous T3, CPS mRNA level, but not CPS activity, also decreased. Additional studies indicated that the TH-induced increase in CPS mRNA was evident within 24 h, could be prevented by simultaneous injection of actinomycin-D, and could not be induced in tadpoles undergoing climax; in this phase the T3 receptors are fully occupied with endogenous TH. When premetamorphic tadpoles were immersed in T3-containing water (0-500 nM) for 6 days, CPS mRNA, CPS activity, and plasma T3 concentration increased in parallel, reaching a maximum at 50 nM. At 50 nM T3, the plasma T3 level was sufficient to saturate the receptors, and no additional increase in CPS mRNA level or CPS activity was obtained at higher concentrations of T3. These studies indicate that the CPS mRNA level during spontaneous development correlates with the plasma T3 concentration and suggest that it is a function of T3 receptor occupancy. The data are also consistent with an effect of TH on transcription of the CPS gene and with a relatively long half-life of its protein product, the CPS enzyme.

Animals↗
PubMed1991

Regulation of c-erbA-alpha messenger RNA species in tadpole erythrocytes by thyroid hormone.

Putative thyroid hormone (TH) nuclear receptors have been detected in several tissues of Rana catesbeiana tadpoles. T3 receptor number (sites per nucleus) in red blood cells (RBCs) and tail increases substantially just before metamorphic climax or in response to exogenous TH; in contrast, receptor number in liver remains relatively constant. TH receptors in mammals and birds are thought to be encoded by a c-erbA gene. In the present study, two c-erbA cDNAs, one prepared from Xenopus laevis oocytes (XenTR alpha 1) and one prepared from Rana catesbeiana tail (RC12), were used to examine the c-erbA-related mRNA species in Rana catesbeiana tissues and determine their role in the TH induction of tadpole RBC receptor number. XenTR alpha 1 encodes a protein with T3-binding properties typical of TH receptors. RC12 is almost 99% homologous with XenTR alpha 1 at the amino acid level and contains all of the putative T3-binding region and most of the DNA-binding region. Using either cDNA as a probe, it was found that two major species of c-erbA-related mRNA species (2.6 and 4.0 kilobases) were clearly evident in tadpole RBCs, tail, and liver. A third, more diffuse band (approximately 5.0 kilobases) was observed in RBC and tail. In RBCs, but not in liver, the combined level of c-erbA-related mRNA species was increased during spontaneous metamorphosis or after administration of TH. Furthermore, the TH-induced increase in both c-erbA-related mRNA species and receptor number in RBCs was prevented if actinomycin-D was administered with TH.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1990

Mechanisms underlying the acceleration of thyroid hormone-induced tadpole metamorphosis by corticosterone.

Adrenal steroids have been shown to accelerate both spontaneous and thyroid hormone (TH)-induced metamorphosis. The present study is concerned with the mechanisms underlying this effect. Premetamorphic Rana catesbeiana tadpoles were immersed in water containing 1-20 nM T4 or T3 +/- 1 microM corticosterone (B) for 6 to 19 days. B is the predominant glucocorticoid in tadpole plasma before climax. As indicated by the rate of tail resorption and hepatic carbamyl phosphate synthetase (CPS) activity, metamorphosis was significantly accelerated when TH-treated animals also received B: after 14 days in T4 (20 nM), tadpole tail length was decreased by 10%; in T4 + B, the decrease was 19%. At the same time, CPS activity was increased approximately 12-fold in tadpoles in T4 and 18-fold in those in T4 + B. Comparable results were obtained when T3 was employed. Neither tail resorption nor CPS activity was influenced by B alone. Plasma T4 levels attained at all bath concentrations of T4 were increased more than 2-fold when B was present. The same was true when T3 was used. In addition, in tadpoles immersed in 20 nM T4, the plasma T3 level-was significantly increased in the presence of B. Assessment of 5'-deiodinase and 5-deiodinase activities in vitro revealed that administration of B for 7 days resulted in a significant increase in 5'-deiodinase activity in skin and a significant reduction in T3 5-deiodinase activity in both liver and gut. Treatment with B reduced the rate of turnover of T3; 72 h after injection of 0.01 nmol [125I]T3, B-treated tadpoles had retained approximately 58% of the dose vs. 42% in controls. T3 nuclear receptor number (sites per nucleus) as assessed by an in vitro saturation technique was not altered in liver, tail, or red blood cells after 14 days of exposure to B. On the basis of these findings it is suggested that the acceleration of TH-induced metamorphosis by B is due at least in part to its ability to increase the plasma level of T4 or T3 through its effects on the peripheral metabolism of TH. HD-09020

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PubMed1989

The role of 3,5,3'-triiodothyronine in the physiological action of thyroxine in the premetamorphic tadpole.

In premetamorphic tadpoles precocious metamorphosis can be induced by immersion in water containing either T4 or T3. T3 5-deiodinase (5D) activity is present in most tissues, and T4 5'-deiodinase (5'D) activity is present in gut and skin; both systems can be inhibited by iopanoic acid (IOP). If conversion of T4 to T3 is important for the normal physiological action of T4 in these tadpoles, it follows that IOP should decrease the effects of T4 and increase those of T3 on metamorphic events. To test this, tadpoles were immersed in water containing either T4 or T3 (20 nM) with or without 1.75 microM IOP. Two indices of metamorphosis, increased leg length and hepatic carbamyl phosphate synthetase activity, were studied. In vehicle- or IOP-treated animals, change in leg length and carbamyl phosphate synthetase activity were minimal. Both indices were increased after exposure to T3 for 10 days or to T4 for 21 days. Moreover, the effects of T3 were significantly enhanced while those of T4 were inhibited when IOP was also present. Both 5'D and 5D activities determined in vitro were inhibited (95% and 60%, respectively) in IOP-treated tadpoles, and this was associated with an increase in the plasma concentration of hormone. In separate experiments, vehicle- and IOP-treated tadpoles received [125I]T4 or [125I]T3 ip. Plasma, liver, gut, and skin were examined 12-24 h later for 125I-labeled products. After [125I]T4 treatment [125I]T3 was found in skin and gut, but not in plasma or liver. After [125I]T3 treatment [125I]3,3'-diiodothyronine was identified in all extracts studied. In vivo generation of these products was reduced by 50% in IOP-treated tadpoles. These findings indicate that generation of T3 from T4 can take place in vivo in the premetamorphic tadpole and strongly support the hypothesis that this process plays an important role in the physiological action of T4 in this species.

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PubMed1988

The ontogeny of iodothyronine 5'-monodeiodinase activity in Rana catesbeiana tadpoles.

Generation of T3 from T4 in vivo cannot be demonstrated in tadpoles until just before metamorphic climax (MC). Possible explanations include the absence of the necessary 5'-monodeiodinase (5'D) process, and/or the presence of an active T3 and T4 5-deiodinase (5D) system before MC. In the present study, 5'D activity was determined in the 12,000 x g supernatent fraction of tissue homogenates prepared from tadpoles in premetamorphosis (PM) and MC (induced by immersion in 2 x 10(-8) M T4) by measuring the 125I-formed from [125I] rT3 or [125I]T4 in the presence of 20 mM dithiothreitol. Eadie-Hofstee plots of data were used to determine maximum velocity and Km. During PM, 5'D activity was undetectable in liver, tail, heart, and kidney, minimal in brain and gut, and could be quantitated only in skin. During MC, 5'D activity was undetectable in liver, heart, and kidney, but was present in tail tissue and was increased more than 5-fold in skin and gut. The increased activity was due to a change in maximum velocity, with no change in Km. In its properties, the tadpole 5'D system was comparable to the type II system found in some mammalian tissues. Thus, it exhibited Km values for T4 and rT3 in the nanomolar range, the preferred substrate was T4, and activity was unaffected by propylthiouracil in the presence of 10 mM dithiothreitol. Under comparable incubation conditions, T3 5D activity was detected in most tissues during PM; the highest activity was found in liver, gut, and kidney. 5D activity was barely detectable in MC. From these studies it is suggested that accumulation of T3 generated from T4 in the tadpole is minimal before MD due to the predominance of 5D activity. During MC, accumulation of T3 is possible because of the substantial increase in 5'D activity together with a marked drop in 5D activity. The principle T3-generating organs appear to be gut, skin, and tail tissue.

Animals↗
PubMed1988

Iodothyronine 5'-deiodinase activity in the amphibian Rana catesbeiana at different stages of the life cycle.

In a previous study, 5' deiodinase (5'D) activity was detected in skin but not in other tissues of premetamorphic tadpoles. When these tadpoles were stimulated to metamorphic climax by treatment with thyroid hormone, activity was increased in skin and was found also in gut and tail tissue. In the present study, 5'D activity was studied at various stages of spontaneous development from early prometamorphosis through metamorphic climax and including the adult frog. 5'D activity was detected in gut and skin at all stages studied and in metamorphosing tail tissue. It was minimal or absent in all other tissues examined. Activity in prometamorphic skin was comparable to that previously observed in premetamorphic skin but increased significantly during metamorphic climax and remained at this level in the adult. 5'D activity was not observed in tail tissue until resorption commenced and when present could not be correlated with tadpole stage or tail length. In both skin and tail, the 5'D activity exhibited values for Michaelis-Menten constant (Km) for rT3 and T4 in the nanomolar range. During prometamorphosis, the 5'D activity in gut exhibited a value for the rT3 Km in the micromolar range. As the tadpoles entered metamorphic climax, the rT3 Vmax of this activity in gut decreased and a second type of 5'D activity, with a Km for rT3 in the nanomolar range, was detected in this tissue. By stage XXI, only the latter component was observed, and its activity increased significantly during metamorphic climax. In the adult frog, 5'D activity in gut was comparable to that seen at the onset of climax. The adult frog also exhibited T3 5D activity in all tissues studied. These observations, together with those reported in the previous study, indicate that gut and skin are the principal T3-generating organs in anuran amphibia and suggest that increased activity of the 5'D system, at the time in the life cycle that the tissues require increased amounts of thyroid hormone, is an important part of thyroid hormone economy in this species.

Aging↗
PubMed1986

Thyroxine and 3,5,3'-triiodothyronine bind to the same putative receptor in hepatic nuclei of Rana catesbeiana tadpoles.

Previous studies have provided conflicting evidence as to whether tadpole liver nuclei contain the same number of high affinity binding sites for T4 as they do for T3. Inability to prepare stable tadpole liver nuclei may have contributed to these inconsistencies. Thus, a study was carried out in which the in vivo binding of T4 and T3 by tadpole liver nuclei was reexamined with a greatly improved method for isolating liver nuclei. It was found that the maximum binding capacities of the nuclei for T3 and T4 were not significantly different [0.161 +/- 0.015 (+/- SEM) vs. 0.185 +/- 0.046 pmol/mg DNA]. However, the affinity of the binding sites for T3 was 2-3 times their affinity for T4 (Kd, 1.65 +/- 0.31 vs. 4.32 +/- 0.92 X 10(-12) M). Furthermore, the nuclear binding of [125I]T4 or [125I]T3 was decreased to comparable levels by administration of saturating amounts of T3 and T4 given either before or with the 125I-labeled hormone, indicating that both hormones were competing for the same set of sites. It is suggested that at least some of the previous conflicting findings related to the number of putative thyroid hormone receptors in tadpole liver nuclei are attributable to inadequate methodology which resulted in an overestimation of the maximum binding capacity for T4.

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PubMed1985

3,5,3'-Triiodothyronine receptors and thyroxine 5'-monodeiodinating activity in thyroid hormone-insensitive amphibia.

Adult anuran Amphibia and neotenous urodeles, such as Necturus maculosus, rarely respond to thyroid hormone (TH). In this study, the possibility was examined that this lack of response is due either to an inability to convert thyroxine (T4) to 3,5,3'-triiodothyronine (T3) or to the absence of nuclear TH receptors. Following injection of [125I]T4, significant amounts of [125I]T3, analyzed by chromatography, were detected in the serum and liver of Necturus and Rana catesbeiana frog indicating that both possesses a T4 5'-monodeiodinating system. Nuclear binding of T3 was studied in suspensions of purified hepatic nuclei and intact red blood cells (RBC). Analysis of binding data revealed that frog liver nuclei contained two sets of saturable T3 binding sets with affinities comparable to those of the two sets of sites previously demonstrated in tadpole liver nuclei (Galton and Schaafsma, 1983). However, the number of sites per nuclei was small compared to tadpole; expressed as pmol/mg DNA, the maximum binding capacity of the high affinity set of sites (MBC1) was 2.2 +/- 0.31 versus 12.9 +/- 1.80 and MBC2 was 24.9 +/- 4.5 versus 42.2 +/- 54. Receptor number in RBC nuclei was also smaller in frog than tadpole: 90 +/- 26 versus 882 +/- 56 sites/nucleus (Kd less than 10(-11) M in both groups). No comparable high affinity binding sites were detected in Necturus liver, but some sites were found in Necturus RBC. These cells contained 2111 +/- 120 sites/nucleus, more than twice the number found in tadpole.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Comparative study of pituitary-thyroid hormone economy in fasting and hypothyroid rats.

Starvation in laboratory rodents results in significant alterations in thyroid hormone economy characterized by decreased circulating levels of thyroxine (T4) and 3,5,3'-triiodothyronine (T3) and a decline in serum thyrotropin (TSH) concentration. To investigate this apparent paradox, we have compared in fasted and hypothyroid animals the intracellular parameters mediating thyroid hormone action in the anterior pituitary gland. In vitro saturation analysis combined with quantitation of nuclear T3 content by radioimmunoassay allowed for characterization of pituitary nuclear T3 receptors and estimation of the endogenous fractional receptor occupancy. In rats, thyroidectomized 4 wk earlier, the 10-fold increase in serum TSH levels and decline in peripheral thyroid hormone concentrations were accompanied by a 61% decrease in pituitary nuclear T3 content and a marked decline in fractional T3 receptor occupancy as compared with control animals. In euthyroid animals subjected to short-term starvation (72 h), serum T3, T4, and TSH levels declined by 52, 43, and 48%, respectively. Despite these marked decreases in circulating thyroid hormone levels, pituitary nuclear T3 content in fasted rats declined by only 15% (P less than 0.05) relative to control levels. This modest decline in nuclear T3 content, combined with a 23% decrease in total T3 receptor number, resulted in an estimated fractional receptor occupancy in fasted animals which was equal to or greater than that noted in controls. The effects of fasting and hypothyroidism on the pituitary were further investigated by quantifying low Michaelis constant (Km) T4 5'-deiodinase activity in the crude cytosol fraction of pituitary homogenates. In thyroidectomized animals, maximum velocity was increased ninefold, whereas fasting resulted in a 37% decrease (P less than 0.025) in this parameter compared with controls. Km values were similar in all experimental groups (4.7 +/- 0.6 nM). These results demonstrate that, despite significant reductions in circulating thyroid hormone concentrations and pituitary T4 5'-deiodinase activity, nuclear T3 levels are maintained at relatively normal levels in the pituitary of the fasted animal and fractional T3 receptor occupancy may actually increase. These findings are in marked contrast to those noted in thyroidectomized animals and suggest that the suppression of TSH secretion accompanying starvation in the rat is mediated, at least in part, by local pituitary mechanisms that serve to maintain and possibly enhance nuclear T3 receptor occupancy.

Animals↗
PubMed1985

Putative nuclear triiodothyronine receptors in tadpole erythrocytes during metamorphic climax.

The characteristics of the nuclear T3 receptors present in red blood cells (RBCs) of Rana catesbeiana tadpoles undergoing metamorphic climax have been investigated with a T3 saturation technique. Because there were significant amounts of receptor-bound endogenous hormone, prolonged incubation in vitro (48 h at 21 C) was necessary to achieve binding equilibrium. Receptor number, which averaged 783 +/- 35 (+/- SE) sites/nucleus during early prometamorphosis (stages XIV-XVI), increased rapidly during the subsequent stages of this phase. By stage XIX, receptor number had reached a maximum of 2464 +/- 152. During climax, receptor number decreased steadily, and by stage XXV, it was lower than that observed during premetamorphosis (stages V-X). This decrease was attributed to the replacement of larval RBCs, which have a high receptor content, by adult RBCs, which possess significantly fewer sites per nucleus. At midclimax, adult and larval RBCs were separated on a Renografin continuous density gradient. Adult cells constituted more than 65% of the total cell population and were shown to contain only 126 +/- 46 sites/nucleus. Although the striking increase in receptor number preceded the substantial increases in plasma T4 and T3 levels that occurred during climax, it was associated with a measurable increase in plasma thyroid hormone levels. Furthermore, receptor number in stage XIV tadpoles was increased markedly after immersion for 14 days in water containing sufficient T3 to raise plasma T3 only to levels normally observed in late prometamorphosis. These findings strongly support the hypothesis that the increases in receptor number and plasma thyroid hormone levels that occur before climax in this species are causally related.

Animals↗
PubMed1985

Putative nuclear triiodothyronine receptors in tadpole liver during metamorphic climax.

It has been shown previously that the maximum binding capacity (MBC) of the putative T3 receptors in tadpole red blood cells (RBCs) is increased during development and can be stimulated by treatment with thyroid hormone (TH). The present study was performed to determine if the MBC of tadpole liver nuclei is also increased during development or after treatment with TH. Because of the relatively high levels of endogenous TH in tadpoles during climax, the use of an in vivo saturation assay employing [125I]T3 was not feasible. Thus, MBC was determined by measuring by RIA the amount of T3 bound to the liver nuclei in tadpoles pretreated with sufficient T3 to saturate the receptors. Values were then corrected for the nonsaturable fraction using data obtained in tadpoles given a large dose of T3 (10 nmol). After this dose, essentially all of the T3 in the nucleus was bound to nonsaturable sites. MBC values estimated by this method and by Scatchard analysis were comparable. In contrast to the observations in tadpole RBCs, no significant change in the MBC of liver nuclei occurred as the tadpole progressed from early prometamorphosis to metamorphic climax; in tadpoles at stages XII-XIV and XIX-XXIII, MBC values were 0.308 +/- 0.024 (+/- SE) and 0.260 +/- 0.035 pmol/mg DNA, respectively. Furthermore, treatment of tadpoles with T4 (1 nmol T4; 14 days before study), which resulted in a marked increase in receptor number in RBCs, had no effect on MBC in hepatic nuclei. The amounts of nucleus-bound endogenous T3 in liver and RBCs were also determined. From these data and the MBC values, it was calculated that hepatic and RBC nuclear receptors were, respectively, 80% and more than 90% occupied with T3. These findings indicate that there is tissue specificity in the response of receptor MBC to TH during metamorphosis, and that most of the TH on the receptor during climax is T3.

Animals↗
PubMed1979

Pituitary-thyroid function of fetuses of hypothyroid and growth hormone treated hypothyroid rats.

Maternal hypothyroidism induced by surgical thyroidectomy (Tx) of the rat resulted in significantly higher fetal serum levels of thyroid stimulating hormone (TSH) and thyroxine (T4) on day 22 of gestation. Surprisingly, administration of growth hormone (GH) to hypothyroid mothers increased further the fetal serum T4 and TSH. The in vitro uptake of 131I-T4 by erythrocytes was elevated significantly when incubated with serum from fetuses of both hypothyroid and hypothyroid GH-treated mothers. Although the plasma protein levels of hypothyroid mothers and their fetuses are decreased significantly as compared to controls this is not true of hypothyroid GH-treated mothers and their fetuses. The T4 levels of both groups of Tx mothers were significantly below that of controls. However, as in the case of their fetuses, the serum T4 of GH-treated hypothyroid mothers was elevated from that of Tx only animals. It is concluded that the pituitary-thyroid system of fetuses of hypothyroid mothers is activated excessively during late gestation, that considerable T4 can be transported from the fetus to the mother during this period and that these fetuses are in fact born in a hyperthyroid state which is aggravated by maternal treatment with GH.

Animals↗
PubMed1978

Role of thyroid gland in oxygen toxicity.

The effects of hyperoxia at ambient pressure on thyroid function and thyroid hormone metabolism have been assessed. Thyroidal activity was depressed in mice and rats by exposure to hyperoxia, due at least in part to a decrease in the rate of secretion of pituitary thyrotropin. The effects of hyperoxia on the peripheral deiodination of thyroxine (T4) were dependent on the concentration of oxygen employed and/or the duration of exposure; exposure to 40--80% oxygen for 96 h resulted in decreases in the rate of deiodination and in the deiodinative clearance of [125I]T4. Hyperoxia also resulted in a marked fall in the serum concentration of endogenous T4 and a decrease in T4-binding activity in serum. Many of these effects of hyperoxia were prevented by the concomitanat administration of large amounts of vitamin E (alpha-tocopherol acetate). These decreases in thyroid function and T4 metabolism were associated with a decrease in the rate of whole body oxygen consumption. Thus, the deleterious effects of oxygen in the rat were not due, even in part, to an oxygen-induced hyperthyroid state in the peripheral tissues.

Animals↗
PubMed1978

Thyroxine: studies concerning its intrinsic physiological activity.

The importance of the monodeiodination of T4 to T3 in the physiological action of T4 was explored by assessing the role of T4 in maintaining prophylthiouracil (PTU)-treated rats during exposure to 4 degrees C. (PTU inhibits both thyroid hormone biosynthesis and T4 to T3 conversion in peripheral tissues.) Firstly, the effects of cold exposure on the metabolism of T4 in control and PTU-treated rats equilibrated with [125I]T4 (2 microgram/100 g b. w./day) were determined. PTU was administered in the food (2 mg/g food). In control rats, no significant changes in T4 metabolism occurred during 3 days at 4 degrees C. Urinary 125I was greatly decreased in PTU-treated rats. Exposure of these rats to cold resulted in some increase but values were still 50% below normal. Secondly, four groups of rats were exposed to cold: control; PTU-treated; T4-treated; PTU + T4-treated. Control and T4-treated rats survived. PTU-treated rats died unless T4 was administered. Radioimmunoassay of T4 and T3 indicated significant concentrations of T3 in sera of rats from all but the PTU + T4 group. These results suggest that T4 permits survival in the cold-exposed PTU-treated rat without being converted to T3 and thus they support the concept that T4 has intrinsic biological activity.

Animals↗