The Peripheral Action of Thyroxine

Tapley, Donald F.; Hatfield, W. B.

doi:10.1016/s0083-6729(08)60719-0

Cited by 8 publications

(6 citation statements)

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“…This conclusion was contrary to the frequently cited mechanisms of action involving direct effects on the efficiency of oxidative phosphorylation or mitochondrial stability, based on work in vitro or after the administration of catabolic doses of thyroid hormones (see [4][5][6][7]. More recent work on amino acid incorporation into mitochondrial protein has also supported the idea that, under conditions close to the physiological, thyroid hormones exert a selective control upon mitochondrial composition without modifying the efficency of oxidative phosphorylation (8)(9)(10).…”

mentioning

confidence: 72%

“…From biochemical studies on skeletal muscle and liver mitochondria, published 2 to 3 years ago, we concluded that the regulation of BMR by thyroid hormones under anabolic conditions could be best explained on the basis of a selective increase in the respiratory and phosphorylative units of the mitochondria (2,3). This conclusion was contrary to the frequently cited mechanisms of action involving direct effects on the efficiency of oxidative phosphorylation or mitochondrial stability, based on work in vitro or after the administration of catabolic doses of thyroid hormones (see [4][5][6][7]. More recent work on amino acid incorporation into mitochondrial protein has also supported the idea that, under conditions close to the physiological, thyroid hormones exert a selective control upon mitochondrial composition without modifying the efficency of oxidative phosphorylation (8)(9)(10).…”

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confidence: 89%

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The Relationship Between the Structure and Activity of Rat Skeletal Muscle Mitochondria After Thyroidectomy and Thyroid Hormone Treatment

Gustafsson

Tata

Lindberg

et al. 1965

The Journal of Cell Biology

211

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The finc structure of rat gastrocncmius muscle fibers has been studied aftcr changes were induced in the basal metabolic rate (BMR) by thyroidectomy and L-thyroxine administration under anabolic conditions. Biochemical analysis of skeletal muscle mitochondrial respiration and phosphorylation from the same tissue preparations has been summarized, details having been published earlier (3). As estimated from electron micrographs, the total amount of mitochondria from thyroidectomized animals was enlarged 1.5 times over that from normal controls. The total amount of mitochondria from thyroidectomized or normal animals made hypermetabolic with thyroxine was increased 2.5 to 3.5 times over that from their corresponding controls. In all cases, there was an increase in the mitochondrial population and the profile ratio of cristae to matrix was also considerably increased, thus indicating both relative and absolute enlargements of the entire surface of the cristae per unit fiber. The major structural changes persisted for at least 3 weeks after the cessation of thyroxine treatment, by which time the elevated mitochondrial respiratory and phosphorylative activity had declined to normal values. The hypertrophy and increase in mitochondrial population was more prominent in the perinuclear and subsacrolemmic regions near blood vessels than in the interstices of the fibrils. The very long interfibrillar mitochondria found in both the hypo-and hypermetabolic tissues are more likely to be derived from outgrowths of the original mitochondria rather than from a fusion of smaller ones. These findings are compatible with the ideas expressed elsewhere (see 1, 3, 10) that, under conditions close to the physiological, thyroid hormones control mitochondrial metabolic activity by a subtle alteration in mitochondrial composition with respect to their respiratory and phosphorylative constituents. ~Ihe possible application of using thyroid hormones in the study of biogenesis of mitochondria and the synthesis of mitochondrial constituents are discussed.

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confidence: 72%

mentioning

confidence: 89%

The Relationship Between the Structure and Activity of Rat Skeletal Muscle Mitochondria After Thyroidectomy and Thyroid Hormone Treatment

Gustafsson

Tata

Lindberg

et al. 1965

The Journal of Cell Biology

211

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“…The (33)(34)(35)(36)(37)(38)(39)(40)(41)(42) has shown a number of changes of possible physiologic significance upon addition of thyroid hormone, including increased mitochondrial protein synthesis in as short an interval as 3 min after addition of T4 or T3 to isolated mitochondria in titro (35). Moreover, Babior, Ingbar, and colleagues have shown increased entry of 14C-labeled adenosine diphosphate into mitochondria after hormone administration (49 (Scatchard plot).…”

Section: Methodsmentioning

confidence: 99%

“…Prior to and throughout the same period of time, however, Tapley and his associates (33)(34)(35)(36)(37)(38)(39)(40)(41)(42) have been accumulating evidence that suggests direct thyroid hormone action upon the mitochondria of responsive cells. Binding of thyroid hormones by rnitochondrial membranes was confirmed by Tata, Ernster, and Suranyi, who reported microsomal and nuclear binding as well (43).…”

mentioning

confidence: 99%

Thyroid hormone binding by a component of mitochondrial membrane.

Sterling¹,

Milch²

1975

Proc. Natl. Acad. Sci. U.S.A.

114

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The thyroid hormone, triiodothyronine, has been shown to be bound by the intranuclear chromatin protein associated with active DNA, where it is believed to stimulate transcription. Evidence exists that the thyroid hormones have direct action not only on nuclei, but also on mitochondria. Therefore, specific proteins that bind thyroid hormones in the mitochondria should be demonstrable.Mitochondria were isolated from homogenized rat livers by sedimentation through 0.25 M sucrose solution, followed by washing four times to free them of microsomes The many recent reports from the laboratories of Oppenheimer (8-15), , and de Groot (5-7) provide evidence of specific nuclear receptors for the thyroid hormones, thyroxine (T4) and triiodothyronine (TS), and suggest that the cell nucleus is a significant locus of hormone action. Indeed, as early as 1966, Siegel and Tobias demonstrated the nuclear localization of thyroid hormone by radioautography of tritium-labeled hormone added to cell cultures of human renal epithelial cells, grown in monolayer (31, 32), an observation which forecast the later developments. These authors showed a diminution of the number of tritium grains over the nucleus if actinomycin D had been added to the cell cultures, but an increase after addition of puromycin, a finding compatible with thyroid hormone action at the transcriptional level in the nucleus.Prior to and throughout the same period of time, however, Tapley and his associates (33-42) have been accumulating evidence that suggests direct thyroid hormone action upon the mitochondria of responsive cells. Binding of thyroid hormones by rnitochondrial membranes was confirmed by Tata, Ernster, and Suranyi, who reported microsomal and nuclear binding as well (43). Perhaps the most striking observation has been the demonstration of increased mitochondrial protein synthesis in as short an interval as 3 min after the addition of T4 or T3 to isolated rat liver mitochondria in vitro (35).Recently we have been studying the binding of T4 and T3 to cell proteins (23,24). The present communication concerns the finding of a protein fraction of the mitochondrial membrane which binds T4 and T3 in the physiological range, and is presumed related to hormonal effect upon energy metabolism.After isolation of mitochondria from rat liver and kidney, the binding of labeled hormones by intact mitochondria was studied, followed by examination of the mitochondrial matrix and membranes, and subsequently protein fractions extracted from the mitochondrial membranes.

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“…Ή γνωστή δρδσις τής θυροξίνης έπί τών μιτοχονδρίων, (αΰξησις κατα ναλώσεως 0 2 ), τουλάχιστον είς φυσιολογικός δόσεις, ερμηνεύεται επί τή βάσει τών τελευταίων παρατηρήσεων καί πάλιν μέσω του μηχανισμού τής πρωτεϊνοσυνθέσεως (σύνθεσις μιτοχονδριακών ενζύμων), δεδομένου δτι α παιτείται λανθάνων χρόνος δια τήν έκδήλωσιν αυτής. Έπί πλέον έχει παρατηρηθή in vitro διόγκωσις τών μιτοχονδρίων, κατόπιν χορηγήσεως τών θυρεοειδικών ορμονών ώς καί άποσύζευξις οξειδωτικής φωσφορυλιώσεως (τελικώς, σχηματισμός ενεργείας άνευ αποθηκεύσεως αυτής) (Tapley et Harfield 1962, Tapley 1964). Καί άλλοι ερευνηταί επίσης έχουν παρατηρή σει μορφολογικάς άλλαγάς εις τά μιτοχόνδρια (Karlson 1967).…”

Section: μηχανισμός δράσεως θυρεοειδικων ορμονώνunclassified

Επιδρασις Της Χλωροπρομαζινης Επι Της Συμπεριφορας Θυρεοτοξικων Επιμ- Υων

Δουκα¹

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Θερμά ευχαριστώ επίσης τον καθηγητή κ. Μενέλαον Μπατρίνον ò οποίος με καθωδήγησεν εις δ,τι άφορα την ένδοκρινολογικήν αποψιν της εργασίας μου. Τον φίλο και συνάδελφον Ί. Στ. Παπαδόπουλον θερμά ευχαριστώ δια την τόσο πολύτιμη βοήθειάν του, καθ' όλον το διάστημα της εκπονήσεως αυτής της διατριβής. Ευχαριστώ πο?ώ επίσης τον συνάδελφο και φίλο Γ. Άθ. Παπαδόπουλον δια το ενδιαφέρον του και τήν βοήθειάν του τήν οποίαν ουδέποτε αρνήθηκε, δσες φορές και αν τήν εζήτησα. Δια συγκεκριμένην βοήθειάν επίσης ευχαριστώ τήν διευθύντριαν τοΰ Άναισθησιολογικοΰ τμήματος τοΰ Νοσοκομείου «Βασιλεύς Παύλος» κ. Σ. Καμβύση-Αέα, τον επιμελητήν τοΰ εργαστηρίου Πειρ. Φαρμακολογίας κ. Π. Κανιάρην, τονέπιμελητήν τοΰ εργαστηρίου 'Υγιεινής κ. Δ. Τόγκον, ώς και τήν παρασκευάστρια τοΰ εργαστηρίου Πειραματικής Φαρμακολογίας δ. Έλ. Καπώνη. 'Ελπίζοντας δτι δεν ελησμόνησα κανένα ευχαριστώ τέλος τήν δ. Μ. Μπαλ*.ταζάνη δια τήν επιμελημένη δακτυλογράφηση τοΰ κειμένου. Ή παροΰσα διατριβή εγένετο κατόπιν ειδικής υποτροφίας προς λήψιν διδακτορικοΰ διπλώματος, εκ τοΰ Ι.Κ.Υ. ('Ιδρύματος Κρατικών Υποτροφιών) κατόπιν διαγωνισμοΰ.

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The Peripheral Action of Thyroxine

Cited by 8 publications

References 188 publications

The Relationship Between the Structure and Activity of Rat Skeletal Muscle Mitochondria After Thyroidectomy and Thyroid Hormone Treatment

The Relationship Between the Structure and Activity of Rat Skeletal Muscle Mitochondria After Thyroidectomy and Thyroid Hormone Treatment

Thyroid hormone binding by a component of mitochondrial membrane.

Επιδρασις Της Χλωροπρομαζινης Επι Της Συμπεριφορας Θυρεοτοξικων Επιμ- Υων

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