Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1985 Aug;120(2):215–221.

Response of the medullary thick ascending limb to hypothyroidism in the rat.

A G Bentley, K M Madsen, R G Davis, C C Tisher
PMCID: PMC1887834  PMID: 4025510

Abstract

Hypothyroidism in the rat is associated with a decrease in kidney size and weight. We have shown previously that this decrease involves all nephron segments in the cortex and outer medulla and is especially pronounced in the medullary thick ascending limb (mTAL). Therefore, the present study was undertaken for examination of the effect of hypothyroidism on the ultrastructure of the rat mTAL. Hypothyroidism was induced by feeding aminotriazole (ATZ), 0.5 g/kg of food, for 4 weeks. A second group of animals received ATZ plus a daily injection of L-thyroxine (T4). A third group was fed a normal diet only and served as control animals. The kidneys were preserved by in vivo perfusion with 3% glutaraldehyde, and tissue from the inner and outer stripe of the outer medulla was processed for electron microscopy. Morphometric analysis revealed a significant decrease in the cross-sectional area of the mTAL in both the inner and outer stripe of the outer medulla in hypothyroid animals. No changes were observed in the surface density of either the apical or basolateral plasma membranes following ATZ treatment. However, when calculated per millimeter tubule, there was a significant decrease in the surface area (SL) of both the apical and basolateral plasma membranes of the mTAL of hypothyroid animals in comparison with control animals. Simultaneous treatment with T4 prevented the ATZ-induced reduction in both tubule cross-sectional area and in the SL of the plasma membrane. These findings suggest that the observed changes in SL of the plasma membrane of the mTAL are due to a regulatory role of thyroid hormone in membrane proliferation as well as in cell growth in general.

Full text

PDF
215

Images in this article

217Figure 1
on p.217
218Figure 2
on p.218
219Figure 3
on p.219

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bradley S. E., Bradley G. P., Stéphan F. Role of structural imbalance in the pathogenesis of renal dysfunction in the hypothyroid rat. Trans Assoc Am Physicians. 1972;85:344–352. [PubMed] [Google Scholar]
  2. Bradley S. E., Stéphan F., Coelho J. B., Réville P. The thyroid and the kidney. Kidney Int. 1974 Nov;6(5):346–365. doi: 10.1038/ki.1974.119. [DOI] [PubMed] [Google Scholar]
  3. Davis R. G., Madsen K. M., Fregly M. J., Tisher C. C. Kidney structure in hypothyroidism. Am J Pathol. 1983 Oct;113(1):41–49. [PMC free article] [PubMed] [Google Scholar]
  4. Discala V. A., Kinney M. J. Effects of myxedema on the renal diluting and concentrating mechanism. Am J Med. 1971 Mar;50(3):325–335. doi: 10.1016/0002-9343(71)90221-x. [DOI] [PubMed] [Google Scholar]
  5. Emmanouel D. S., Lindheimer M. D., Katz A. I. Mechanism of impaired water excretion in the hypothyroid rat. J Clin Invest. 1974 Oct;54(4):926–934. doi: 10.1172/JCI107833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fregly M. J. Effect of aminotriazole on thyroid function in the rat. Toxicol Appl Pharmacol. 1968 Nov;13(3):271–286. doi: 10.1016/0041-008x(68)90101-4. [DOI] [PubMed] [Google Scholar]
  7. Hall D. A., Varney D. M. Effect of vasopressin on electrical potential difference and chloride transport in mouse medullary thick ascending limb of Henle's loop. J Clin Invest. 1980 Oct;66(4):792–802. doi: 10.1172/JCI109917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hebert S. C., Culpepper R. M., Andreoli T. E. NaCl transport in mouse medullary thick ascending limbs. II. ADH enhancement of transcellular NaCl cotransport; origin of transepithelial voltage. Am J Physiol. 1981 Oct;241(4):F432–F442. doi: 10.1152/ajprenal.1981.241.4.F432. [DOI] [PubMed] [Google Scholar]
  9. Holmes E. W., Jr, DiScala V. A. Studies on the exaggerated natriuretic response to a saline infusion in the hypothyroid rat. J Clin Invest. 1970 Jun;49(6):1224–1236. doi: 10.1172/JCI106336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Imbert-Teboul M., Chabardès D., Montégut M., Clique A., Morel F. Vasopressin-dependent adenylate cyclase activities in the rat kidney medulla: evidence for two separate sites of action. Endocrinology. 1978 Apr;102(4):1254–1261. doi: 10.1210/endo-102-4-1254. [DOI] [PubMed] [Google Scholar]
  11. Katz A. I., Emmanouel D. S., Lindheimer M. D. Thyroid hormone and the kidney. Nephron. 1975;15(3-5):223–249. doi: 10.1159/000180514. [DOI] [PubMed] [Google Scholar]
  12. Katz A. I., Lindheimer M. D. Renal sodium- and potassium-activated adenosine triphosphatase and sodium reabsorption in the hypothyroid rat. J Clin Invest. 1973 Apr;52(4):796–804. doi: 10.1172/JCI107243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kriz W., Bankir L. ADH-induced changes in the epithelium of the thick ascending limb in Brattleboro rats with hereditary hypothalamic diabetes insipidus. Ann N Y Acad Sci. 1982;394:424–434. doi: 10.1111/j.1749-6632.1982.tb37454.x. [DOI] [PubMed] [Google Scholar]
  14. Lo C. S., Gerendasy D., Lo T. N. Effect of triiodothyronine on renal growth and renal sodium reabsorption in hypothyroid rats. Pflugers Arch. 1981 May;390(2):186–190. doi: 10.1007/BF00590205. [DOI] [PubMed] [Google Scholar]
  15. Lo C. S., Lo T. N. Time course of the renal response to triiodothyronine in the rat. Am J Physiol. 1979 Jan;236(1):F9–13. doi: 10.1152/ajprenal.1979.236.1.F9. [DOI] [PubMed] [Google Scholar]
  16. Michael U. F., Barenberg R. L., Chavez R., Vaamonde C. A., Papper S. Renal handling of sodium and water in the hypothyroid rat. Clearance and micropuncture studies. J Clin Invest. 1972 Jun;51(6):1405–1412. doi: 10.1172/JCI106936. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Michael U. F., Kelley J., Alpert H., Vaamonde C. A. Role of distal delivery of filtrate in impaired renal dilution of the hypothyroid rat. Am J Physiol. 1976 Mar;230(3):699–705. doi: 10.1152/ajplegacy.1976.230.3.699. [DOI] [PubMed] [Google Scholar]
  18. Morel F. Sites of hormone action in the mammalian nephron. Am J Physiol. 1981 Mar;240(3):F159–F164. doi: 10.1152/ajprenal.1981.240.3.F159. [DOI] [PubMed] [Google Scholar]
  19. Sasaki S., Imai M. Effects of vasopressin on water and NaCl transport across the in vitro perfused medullary thick ascending limb of Henle's loop of mouse, rat, and rabbit kidneys. Pflugers Arch. 1980 Feb;383(3):215–221. doi: 10.1007/BF00587521. [DOI] [PubMed] [Google Scholar]
  20. Scammell J. G., Fregly M. J. The effect of 3-amino-1,2,4-triazole on hepatic and renal deiodination of L-thyroxine to 3,5,3'-triiodothyronine. Toxicol Appl Pharmacol. 1981 Aug;60(1):45–51. doi: 10.1016/0041-008x(81)90133-2. [DOI] [PubMed] [Google Scholar]
  21. Vaamonde C. A., Michael U. F., Oster J. R., Sebastianelli M. J., Vaamonde L. S., Klingler E. L., Jr, Papper S. Impaired renal concentrating ability in hypothyroid man. Nephron. 1976;17(5):382–395. doi: 10.1159/000180744. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES