Mechanism of action of thyroid hormones on erythrocyte 2,3-diphosphoglyceric acid synthesis

Snyder, Lois; Reddy, William J.

doi:10.1172/jci106419

Cited by 73 publications

(23 citation statements)

References 15 publications

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“…Our findings of unaltered baseline TSH concentration, but elevated levels of both total and free fractions of T3 and T4 are consistent with most of the previous studies (8,12,22,30,31,39,43), suggesting that a slight hyperthyroidism may be necessary to withstand the extreme environments of high altitude (4). Thyroid hormones increase the levels of 2,3-diphosphoglyceric acid in erythrocytes, facilitating oxygen release to the tissues, by causing a shift of the oxyhemoglobin dissociation curve to the right, advantageous in hypoxia (42). Several explanations for the TSH-independent T4 rise have been proposed.…”

Section: Discussionsupporting

confidence: 92%

Effects of high-altitude hypoxia on the hormonal response to hypothalamic factors

Richalet

Letournel

Souberbielle

2010

American Journal of Physiology-Regulatory, Integrative and Comp

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Acute and chronic exposure to high altitude induces various physiological changes, including activation or inhibition of various hormonal systems. In response to activation processes, a desensitization of several pathways has been described, especially in the adrenergic system. In the present study, we aimed to assess whether the hypophyseal hormones are also subjected to a hypoxia-induced decrease in their response to hypothalamic factors. Basal levels of hormones and the responses of TSH, thyroid hormones, prolactin, sex hormones, and growth hormone to the injection of TRH, gonadotropin-releasing hormone, and growth hormone-releasing hormone (GHRH) were studied in eight men in normoxia and on prolonged exposure (3-4 days) to an altitude of 4,350 m. Thyroid hormones were elevated at altitude (+16 to +21%), while TSH levels were unchanged, and follicle-stimulating hormone and prolactin decreased, while leutinizing hormone was unchanged. Norepinephrine and cortisol levels were elevated, while no change was observed in levels of epinephrine, dopamine, growth hormone (GH), IGF-1, and IGFBP-3. The mean response to hypothalamic factors was similar in both altitudes for all studied hormones, although total T4 was lower in hypoxia during 45 to 60 min after injection. The effect of hypoxia on the hypophyseal response to hypothalamic factors was similar among subjects, except for the GH response to GHRH administration. We conclude that prolonged exposure to high-altitude hypoxia induces contrasted changes in hormonal levels, but the hypophyseal response to hypothalamic factors does not appear to be blunted.

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Section: Discussionsupporting

confidence: 92%

Effects of high-altitude hypoxia on the hormonal response to hypothalamic factors

Richalet

Letournel

Souberbielle

2010

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Incubation of normal erythrocytes with physiological concentrations of thyroid hormone increases their 2,3-DPC content. The effect was detected within 5 min and was maximal after 40 min Snyder et al, 1970). Positive results were also obtained with partially purified preparations of DPG-mutase, suggesting that thyroid hormone may directly affect the activity of the enzyme.…”

Section: Direct Effects Of Thyroid Hormonementioning

confidence: 77%

The Action of Thyroid Hormone

Bernal

Refetoff

1977

Clinical Endocrinology

104

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SUMMARYThyroid hormone affects both developmental and metabolic processes. It has a relatively specific effect on the synthesis of a number of enzymes and other proteins. The fundamental cellular mechanism of action seems to be at the level of genetic regulation. It involves interaction with nuclear receptors, leading to an activation of the protein synthesizing machinery. How binding to receptors is coupled to genetic activation is completely unknown. At least part of the metabolic effects of thyroid hormone could be mediated through an interaction with mitochondria and cell membrane, and with some enzymatic systems such as adenylcyclase.

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“…In whole blood and in purified erythrocytes, Miller et al [7], Snyder and Reddy [8, 9]and Kondo et al [10]found that T 3 increased 2,3-BPG levels. In contrast, Rose [11], Duhm and Gerlach [12], Czernik et al [13]and Torrance [14]reported that 2,3-BPG concentration was not altered under hyperthyroidism.…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that T 3 increases 2,3-BPG levels as a consequence of a direct effect of the hormone on BPGS activity [7, 8, 9, 10]. However, other studies showed no changes, or even a decrease, in 2,3-BPG levels under hyperthyroid conditions [11, 12, 13, 14, 15].…”

Section: Introductionmentioning

confidence: 99%

Effects of Thyroid Hormone and Hypoxia on 2,3-Bisphosphoglycerate, Bisphosphoglycerate Synthase and Phosphoglycerate Mutase in Rabbit Erythroblasts and Reticulocytes in vivo

González-Cinca

Ossa²,

Carreras³

et al. 2004

Horm Res Paediatr

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Objectives: The effects of triiodothyronine (T₃) and hypoxia on 2,3-bisphosphoglycerate (2,3-BPG) studied in vitro are unclear. To clarify these effects we selected a more physiologic approach: the in vivo study in rabbits. We also present the changes produced by T₃ and hypoxia on phosphoglycerate mutase (PGAM), which requires 2,3-BPG as a cofactor, and 2,3-BPG synthase (BPGS), the enzyme responsible for 2,3-BPG synthesis in erythroblasts and reticulocytes. Methods: Hyperthyroidism was induced by daily T₃ injection (250 µg/kg), hypoxia by a mixture of 90% nitrogen and 10% oxygen and hypothyroidism by propylthiouracil (PTU) added to drinking water. Results: Both T₃ administration and hypoxic conditions increased 2,3-BPG levels and BPGS mRNA levels and activity in erythroblasts but not in reticulocytes. Unlike BPGS, both PGAM mRNA levels and activity were increased in erythroblasts and reticulocytes under hyperthyrodism and hypoxia. The antihormone PTU produced opposite effects to T₃. Conclusion: The results presented here suggest that both hyperthyroidism and hypoxia modulate in vivo red cell 2,3-BPG content by changes in the expression of BPGS. Similarly, the changes in PGAM activity are also explained by changes in its expression.

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Mechanism of action of thyroid hormones on erythrocyte 2,3-diphosphoglyceric acid synthesis

Cited by 73 publications

References 15 publications

Effects of high-altitude hypoxia on the hormonal response to hypothalamic factors

Effects of high-altitude hypoxia on the hormonal response to hypothalamic factors

The Action of Thyroid Hormone

Effects of Thyroid Hormone and Hypoxia on 2,3-Bisphosphoglycerate, Bisphosphoglycerate Synthase and Phosphoglycerate Mutase in Rabbit Erythroblasts and Reticulocytes in vivo

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