Action of Thyroid Hormones on Brain Metabolism of Newborn Rats

Reiss, Jean M.; Reiß, M.; Wyatt, Audrey

doi:10.3181/00379727-93-22650

Cited by 26 publications

(8 citation statements)

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“…Additional studies are required to resolve this issue. The suggestion that O2 consumption in neonatal brain, in contradistinction to that in the adult organ, is responsive to thyroid hormones (26), however, seems unlikely on the basis of preliminary evidence from our laboratory (27).…”

Section: Discussionmentioning

confidence: 84%

Nuclear Triiodothyronine Receptor Sites in Brain: Probable Identity with Hepatic Receptors and Regional Distribution*

1978

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Studies were undertaken to compare the physicochemical characteristics of solubilized nuclear T 3 receptors obtained from rat liver and brain and to establish the regional distribution of receptor sites in various areas of the brain. Scatchard analysis revealed that nuclear receptors from brain and liver had similar equilibrium association constants (2.3 ± 0.51 and 1.8 ± 0.54 X 10'° M~', respectively). Simultaneous chromatography of mixed extracts of the soluble receptor sites on DEAE-Sephadex A-50 resulted in an identical elution pattern with a single peak at 0.15 M NaCl in a continuous saline gradient. Indistinguishable sedimentation patterns were observed on a 5-20% sucrose gradient. The relative affinities of several analogs of T3 including L-T 4 , 3'-isopropyl-3,5-L-diiodothyronine, 3,3'-5-triiodothyroacetic acid, and L-rT 3 were nearly identical. These findings suggest that the nuclear T 3 receptor in brain and liver are the same. The concentrations of T3 specifically bound to nuclear sites in various regions of the brain were studied by in vivo displacement techniques. The cortex contained the highest concentration (0.73 ng T 3 /mg DNA). The hypothalamus and telencephalon bound approximately 0.1-0.2 ng T 3 /mg DNA, whereas the cerebellum contained the lowest concentration of T3 (0.016 ng/mg DNA). A low concentration of receptor sites per mg DNA in cerebellum as compared to the cerebrum was confirmed with in vitro studies of nuclear extracts. The low concentration of receptors per mg DNA in the cerebellum is probably due to a significantly reduced concentration of receptors in the tightly packed granule cells, which constitute the bulk of cell types in this tissue and account for the high concentration of DNA per g tissue. Other cell types, such as the Purkinje cell, may therefore still contain a substantial number of receptor sites and constitute a target for thyroid hormone action. (Endocrinology 103: 267, 1978) S INCE the initial description and characterization of specific binding sites for triiodothyronine (L-T3) in rat hepatic nuclei (1), evidence has accumulated from several laboratories which strongly suggests these sites are the points of initiation of hormonal action. In the intact animal, the tissue response to administration of hormone is apparently limited by the occupation of these sites (2). Similarly, Samuels has demonstrated in GHi cells in tissue culture that the dissociation constant (kd) of the nuclear sites is nearly the same as the dose required for half-maximal stimulation of GH synthesis (3). Further, a large series of analogs of T3 have been tested both in vivo (4) and in vitro (5) for their ability to displace T3 from these sites. The relative binding affinities correlated well with the relative thyro-

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Section: Discussionmentioning

confidence: 84%

Nuclear Triiodothyronine Receptor Sites in Brain: Probable Identity with Hepatic Receptors and Regional Distribution*

1978

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“…Nevertheless, as indicated in Fig. 4, T3 failed to increase oxygen consumption either in the neonatal or in the adult animal despite the use of multiple dosage regimens including the one used by Reiss et al (61). Since many of the well-established T3-induced changes in brain cytoarchitecture occur in rats within the first 14 days after birth, it is reasonable to assume that the neonatal brain is sensitive to T3 and to conclude that oxygen consumption is not an appropriate parameter for measuring thyroid hormone action in this tissue.…”

Section: Some General Principles Of Thyroid Hormone Actionmentioning

confidence: 89%

Thyroid Hormone Action at the Cellular Level

Oppenheimer

1979

Science

501

169

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A large body of circumstantial evidence suggests that the basic unit of thyroid hormone action is the triiodothyronine nuclear receptor complex. This complex stimulates the formation, directly or indirectly, of a diversity of messenger RNA (mRNA) sequences. A generalized increase in mRNA as well as a disproportionate increase in a limited number of RNA sequences have been demonstrated. Regulation of thyroid hormone effects may be carried out largely at a local cellular level. Highly selective alterations in sensitivity to the triiodothyronine nuclear receptor complex may occur at specific target genes. Metabolic factors and hormones participate in such regulation. In a given tissue, alterations in the total number of receptor sites has not been shown to be useful as an index of thyroid hormone response, and local modulation of the response to the triiodothyronine receptor complex by a variety of factors other than triiodothyronine may be carried out at a postreceptor level.

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“…In contrast with the adult brain, initial reports suggested that the administration of thyroid hormone to euthyroid neonatal rats increases oxygen consumption in the brain (Fazekas et al. 1951; Reiss et al. 1956), but later reports failed to reproduce these data (Holtzman and Moore 1977; Schwartz and Oppenheimer 1978) and therefore mitochondrial function has been considered insensitive to the action of this hormone in the brain.…”

mentioning

confidence: 99%

Thyroid hormone regulates oxidative phosphorylation in the cerebral cortex and striatum of neonatal rats

Martínez¹,

Hoyo²,

Martı́n³

et al. 2001

Journal of Neurochemistry

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We have previously shown that thyroid hormone (T 3 ) regulates mitochondrial gene expression, morphology and transmembrane potential in the developing brain. Here, we have analysed the effect of thyroid hormone on mitochondrial function in different brain regions. For this purpose we have determined, in control, hypothyroid and T 3 -treated hypothyroid neonatal rats, the rate of oxidative phosphorylation in isolated mitochondria and the activity of the respiratory complexes in tissue homogenates. Our results showed a decrease in oxidative phosphorylation rate (only in the presence of NADH-generating substrates) and mitochondrial complexes I and III activity in the cerebral cortex and striatum of hypothyroid neonates, but not in the other areas analysed (hippocampus, cerebellum, thalamus, mid brain and brain stem). In parallel with mitochondrial activity, the levels of mitochondrially encoded transcripts were decreased only in the cerebral cortex and striatum of hypothyroid rats. The administration of T 3 corrected all these parameters. In summary, this study showed a down-regulation of mitochondrial gene expression accompanied by a decrease in mitochondrial activity in the cerebral cortex and striatum of developing hypothyroid neonatal rats.

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Action of Thyroid Hormones on Brain Metabolism of Newborn Rats

Cited by 26 publications

References 0 publications

Nuclear Triiodothyronine Receptor Sites in Brain: Probable Identity with Hepatic Receptors and Regional Distribution*

Nuclear Triiodothyronine Receptor Sites in Brain: Probable Identity with Hepatic Receptors and Regional Distribution*

Thyroid Hormone Action at the Cellular Level

Thyroid hormone regulates oxidative phosphorylation in the cerebral cortex and striatum of neonatal rats

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