Pflügers Archiv

, Volume 394, Issue 4, pp 294–301 | Cite as

Tubular transport processes in proximal tubules of hypothyroid rats. Lack of relationship between thyroidal dependent rise of isotonic fluid reabsorption and Na+−K+-ATPase activity

  • Natale G. De Santo
  • Giovambattista Capasso
  • Rolf Kinne
  • B. Moewes
  • Carlo Carella
  • Pietro Anastasio
  • Carmelo Giordano
Transport Processes, Metabolism and Endocrinology; Kidney, Gastrointestinal Tract, and Exocrine Glands


Hypothyroid rats reconstituted with 10 μg/kg b.w. per day of tri-iodothironine (T3) for 4 days resulted in normal free T3 and TSH levels. FT3 levels were: 0.53±0.3 pg/ml in hypothyroid rats; 2.78±1.21 pg/ml in hormone reconstituted rats and 2.90±0.90 pg/ml in euthyroid rats. TSH levels were 3,508±513 μg/ml in hypothyroid rats; 1,008±204 μg/ml in reconstituted rats and 270±184 ng/ml in euthyroid rats.

When hypothyroid rats were reconstituted with 50 μg T3/kg b.w. per day, TSH levels were nearly normal after 4 days (1,157±621 ng/ml). However FT3 levels after 1–4 days were always higher than in euthyroid rats.

Hypothyroid rats show a decrease in isotonic fluid reabsorption (Jv) in the proximal tubule (1.50±0.08 versus 4.96±0.23 10−2 nl·mm−1·s−1 in euthyroid animals). 1 day after T3 (10 μg/kg b.w./day) injectionJv was increased significantly to 2.05±0.20 10−2 nl·mm−1·s−1 and continued to increase during 4 days of T3 reconstitution.

When 50 μg T3/kg b.w./day was used,Jv increased to 2.75±0.07 after 1 day and to 3.10±0.42 10−2 nl·mm−1·s−1 after 4 days.Jv was never reaching a value close to that of euthyroid rats because the tubular radius in hypothyroid rats (14.7±1.8 μm) is less than that of euthyroid rats (19.2±0.5 μm). The radius in hypothyroid rats treated with T3 was unchanged over a 4 day course with either high or low doses of T3.

Na+−K+-ATPase activity was found to be 2.91±0.16 μM Pi/h×mg protein in homogenates of kidney cortex from hypothyroid rats. Treatment of hypothyroid rats with 10 μg or 50 μg of T3 resulted in an initial decrease in ATPase activity, followed by an increase to base level in hypothyroid rats with 10 μg and a significantly higher level with 50 μg. This decrease in ATPase activity was contrasted to the increase inJv.

These data indicate that there is a dissociation between the effects of physiological doses of thyroid hormones on proximal tubular reabsorption and the effects of T3 on Na+−K+-ATPase activity of kidney cortex. This leads to question the relationship between sodium transport and ATPase activity under physiological doses of thyroid hormones. An early effect of physiological doses of thyroid hormones on brush border Na+ permeability is suggested.

Key words

Thyroid gland Proximal tubular transport Na+−K+-ATPase 


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  1. 1.
    Adamson LF, Ingbar SH (1967) Selective alterations by triiodothyronine of amino acid transport in embryonic bone. Endocrynology 81:1362–1371Google Scholar
  2. 2.
    Asano Y, Liberman AU, Edelman IS (1976) Thyroid thermogenesis: relationship between Na+ dependent respiration and Na+−K+-adenosine triphosphatase activity in rat skeletal muscle. J Clin Invest 57:368–379Google Scholar
  3. 3.
    Berner W, Kinne R (1976) Transport of p-aminohippuric acid by plasma membrane vesicles from rat kidney cortex. Pflügers Arch 361:269–277Google Scholar
  4. 4.
    Capasso G, Kinne R, Moewes B, Anastasio P, De Santo NG, Giordano C (1982) Thyroidal regulation of alkaline phosphatase activity in kidney cortex brush border membranes. Renal Physiol 5:206–208Google Scholar
  5. 5.
    De Santo NG, Capasso G, Paduano C., Carella C, Giordano C (1980) Tubular transport processes in proximal tubules of hypothyroid rats. Micropuncture studies on isotonic fluid, amino acid and buffer reabsorption. Pflügers Arch. 384:117–122Google Scholar
  6. 6.
    De Santo NG, Capasso G, Paduano C, Giordano C (1980) Sodium transport in the proximal tubule of hypothyroid rats. In: Leaf A, Giebish G (eds) Renal pathophysiology, Raven Press, New York, pp 269–273Google Scholar
  7. 7.
    Doucet A, Katz AI (1981) Short term effect of aldosterone on Na−K-ATPase in single nephron segments. Am J Physiol 241:F273-F278Google Scholar
  8. 8.
    Emmanouel DS, Lindheimer MD, Katz AI (1974) Mechanism of impaired water excretion in the hypothyroid rat. J Clin Invest 54:926–934Google Scholar
  9. 9.
    Gertz KH (1963) Transtubulare Natriumchloridflüsse und Permeabilität für Nichtelektrolyte in proximalen und distalen Konvolut der Rattenniere. Pflügers Arch 276:336–356Google Scholar
  10. 10.
    Gibbs GE, Reimer K (1965) Quantitative microdetermination of enzymes in seat glands. III. Succinic dehydrogenase in cystic fibrosis. Proc Soc Expt Biol Med 119:470–478Google Scholar
  11. 11.
    Goldfine ID, Simons CG, Ingbar SH (1975) Stimulation of the uptake of α-aminoisobutyric acid in rat thymocites byl-triiodothyronine: a comparison with insulin and dibutyryl ciclic AMP. Endocrinology 96:802–805Google Scholar
  12. 12.
    Gruber WD, Knauf H, Fromter E (1973) The action of aldosterone on Na+ and K+ transport in the rat submaxillary main duct. Pflügers Arch 344:33–49Google Scholar
  13. 13.
    Gyory AZ (1971) Reexamination of the split oil droplet as applicated to kidney tubules. Pflügers Arch 324:328–343Google Scholar
  14. 14.
    Heidrich HG, Kinne R, Kinne-Saffran E, Hanning K (1972) The polarity of the proximal tubule cell in rat kidney. J Cell biol 54:232–245Google Scholar
  15. 15.
    Hierholzer K, Wiederholt M (1976) Some aspect of distal tubular solute and water transport. Kidney Int 9:198–213Google Scholar
  16. 16.
    Holmes, EW, Di Scala VA (1970) Studies on the exagerated natriuretic response to a saline infusion in the hypothyroid rat. J Clin Invest 49:1224–1236Google Scholar
  17. 17.
    Katz AI, Lindheimer MD (1973) Renal sodium and potassium activated adenosine triphosphatase and sodium reabsorption in the hypothyroid rat. J Clin Invest 52:976–804Google Scholar
  18. 18.
    Koefoed-Johnsen V, Ussing HH (1958) The nature of frog skin potential. Acta Physiol Scand 42:298Google Scholar
  19. 19.
    Kraus H, Kinne R (1970) Regulation der bei langdauerndem körperlichen Training beobachteten metabolischen Adaptation und Leistungssteigerung durch Thyreoidhormone. Pflügers Arch 321:332–345Google Scholar
  20. 20.
    Ismail-Beigi F, Edelman S (1970) Mechanism of thyroid thermogenesis: role of active sodium transport. Proc Natl Acad Sci USA 67:1071–1079Google Scholar
  21. 21.
    Ismail-Beigi F, Edelman IS (1971) The mechanism of calorigenic action of thyroid hormone. Stimulation of Na+−K+-activated adenosinetriphosphatase. J Gen Physiol 57:710–722Google Scholar
  22. 22.
    Ismail-Beigi F, Edelman IS (1974) Time course of the effect of thyroid hormone on respiration and Na+−K+-ATPase activity in rat liver. Proc Soc Expt Biol Med 146:983–988Google Scholar
  23. 23.
    Ismail-Beigi F, Bissel DM, Edelman IS (1976) Thyroid thermogenesis in adult rat hepatocytes in primary monolayer culture. Direct action of thyroid hormone in vitro. J Gen Physiol 73:369–383Google Scholar
  24. 24.
    Liberman UA, Asano Y, Lo CS, Edelman IS (1971) Relationship between Na+-dependent respiration and Na+−K+-adenosine triphosphatase activity in the action of thyroid hormone on rat jejunal mucosa. Biophys J 27:127–144Google Scholar
  25. 25.
    Lo CS, Lo NT (1979) Time course of renal response to triiodothyronine in the rat. Am J Physiol 236:F9-F13Google Scholar
  26. 26.
    Lo CS, Lo NT (1980) Effect of tri-iodothyronine on the synthesis and degradation of the small subunit of renal cortical (Na+−K+)-adenosine triphosphatase. J Biol Chem 225:2131–2136Google Scholar
  27. 27.
    Lo CS, August TR, Liberman UA, Edelman IS (1976) Dependence of renal (Na+−K+)-adenosine triphosphatase activity on thyroid status. J Biol Chem 251:7826–7833Google Scholar
  28. 28.
    Lo CS, Cheng W, Klein LE (1981) Effect of triiodothyronine on (Na++K+)-adenosine triphosphatase and (Na++Mg2+)-dependent phosphorylated intermediate in rat salivary glands. Pflügers Arch 392:134–138Google Scholar
  29. 29.
    Lowry OH, Rosebrough MJ, Farr AL, Randal RJ (1951) Protein measurement with the Folin reagent. J Biol Chem 193:265–275Google Scholar
  30. 30.
    Michael UF, Baremberg RL, Chavez R, Vaamonde CA, Papper S (1972) Renal handling of sodium, water in the hypothyroid rat. (Clearance and micropuncture studies). J Clin Invest 51:1405–1412Google Scholar
  31. 31.
    Philipson KD, Edelman IS (1977) Phyroid hormone control of Na+−K+-ATPase and K+ dependent phosphatase in rat heart. Am J Physiol 232:C196-C201Google Scholar
  32. 32.
    Pliam NB, Goldfine ID (1977) High affinity thyroid hormone binding sites on purified rat liver plasma membranes. Biochem Biophys Res Commun 79:166–172Google Scholar
  33. 33.
    Reichlin S, Martin BJ, Boshans RL, Schalch DS, Pierce JG, Bollinger J (1970) Measurement of THS in plasma and pituitary of the rat radioimmunoassay bovine TSH: the effect of thyroidectomy and thyroxine administration on plasma TSH levels. Endocrinology 87:1022–1031Google Scholar
  34. 34.
    Schoner W, von Ilberg C, Kramer R, Seubert W (1976) On the mechanism of Na+ and K+ stimulated hydrolysis of adenosine triphosphate. 1. Purification and properties of a Na+ and K+-activated ATPase from ox brain. Eur J Biochem 1:334–343Google Scholar
  35. 35.
    Segal J, Gordon A, Gross J (1976) Evidence thatl-triiodothyronine (T3) exerts its biological action not only through its effect on nuclear activity. In: Robbins J, Robbins LE (eds) Thyroid research. American Elsevier, New York, pp 331–333Google Scholar
  36. 36.
    Silva P, Torretti J, Hayselett JP, Epstein FH (1976) Relation between Na+−K+-ATPase activity and respiration in the rat kidney. Am J Physiol 230:1432–1438Google Scholar
  37. 37.
    Stephan F, Jahn H, Reville P, Urban M (1963) Action de l'insuffisance thyroidienne chronique sur le debit urinaire et le pouvoi de concentration de rein chez le rat Rev Franc Etudes Clin Biol 8:890–899Google Scholar
  38. 38.
    Sterling K (1979) Thyroid hormone action at the cell level. New Engl J Med 300:117–123Google Scholar
  39. 39.
    Taylor RE Jr, Fregly JM (1965) Renal response to propylthiouracil-treated rats to injected mineralcorticoids. Endocrinology 75:33–38Google Scholar
  40. 40.
    Tata JR, Widnell CC (1966) Ribonucleic acid synthesis during the early action of thyroid hormones. Biochem J 98:604–620Google Scholar
  41. 41.
    Ullrich KJ (1980) Mode of inhibition of proximal renal transport processes. In: Leaf A, Giebish G (eds) Renal Pathophysiology. Raven Press, New YorkGoogle Scholar

Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • Natale G. De Santo
    • 1
  • Giovambattista Capasso
    • 1
  • Rolf Kinne
    • 2
  • B. Moewes
    • 2
  • Carlo Carella
    • 1
  • Pietro Anastasio
    • 1
  • Carmelo Giordano
    • 1
  1. 1.Chairs of Nephrology and Pediatric NephrologyFirst Faculty of Medicine and Surgery University of NaplesNaplesItaly
  2. 2.Max-Planck-Institut für BiophysikFrankfurt am MainGermany

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