Sites of thyroid hormone action on Na?K-ATPase along the rabbit nephron

Abstract

Although Ismail-Beigi and Edelman demonstrated in 1971 that thyroid hormones control the activity of Na-K-ATPase in the mammalian kidney, the actual site of this regulation inside the organ was not located. We therefore decided to study the relationship between thyroid hormones and Na-K-ATPase activity in individual nephron segments obtained by microdissection of collagenase-treated rabbit kidneys. For this purpose, the changes in the activity and number of catalytic sites of Na-K-ATPase in response to thyroidectomy or triiodothyronine administration were examined. Eight to 12 days after thyroidectomy, Na-K-ATPase activity had dropped by 40 to 80% in the convoluted and straight portions of the proximal tubules, and in the cortical and outer medullary collecting tubules, but not in the thick ascending limbs of Henle's loops or distal convoluted tubules. The apparent number of catalytic sites for Na-K-ATPase, as measured by specific binding of 3H-ouabain, decreased in parallel with Na-K-ATPase activity, and therefore this enzyme's specific activity was not altered. Fourty eight hours after injection of thyroidectomized animals with a single dose of either 100 or 500 micrograms/kg triiodothyronine, Na-K-ATPase activity in target segments was restored to the level measured in control animals. These effects of thyroid hormone were specific for Na-K-ATPase, since the activity of adenylate cyclase, another marker of the basolateral membrane, was not altered by thyroidectomy. The results obtained indicate that triiodothyronine controls Na-K-ATPase activity in specific nephron segments, by altering the number of this enzyme's catalytic sites.

Thyroid hormone modulates ClC-2 chloride channel gene expression in rat renal proximal tubules

“…More detailed analysis, using RT-PCR on isolated nephronal segments as well as cultured proximal tubule cells, showed that the results of RPA were attributable to the modulation of ClC-2 message only in rat PCT and PST respectively. The specific thyroid hormones action in proximal tubules is consistent with the fact that this nephron segment has the greatest density of thyroid hormone receptors and is thus more responsive to the action of thyroid hormones (Barlet et al 1995). This characteristic of the proximal tubule may be due to its high metabolic activity, an attribute that is necessary for its role in transporting ions and hence 70% of the total filtered fluid (Capasso et al 1999).…”

“…Thyroid hormones has been shown to increase fluid reabsorption in rat proximal tubules (Capasso et al 1999). Importantly, thyroid hormone modulates the expression of Na + /K + ATPase mRNA and protein, and hence regulates the activity of this critical component of renal sodium transport (McDonough et al 1988, Azuma et al 1993, Barlet et al 1995. In proximal tubule, thyroid hormone acts on the Na + /H + exchanger to change intratubular acidification dynamics (Morales et al 1997).…”

The Thyroid and the Kidney: A Complex Interplay in Health and Disease

“…Hypothyroidism is associated with a decrease in transporter function and the opposite occurs (7) decreased (7) Peripheral vascular resistance decreased (7) increased (7) RAS activity increased (17) decreased (17) RBF increased (49) decreased (48,49) Glomerular vasoconstriction decreased (53) increased (50,51) Glomerular surface area increased (48) decreased (26) Tubulo-glomerular feedback increased (54) increased (49) Filtration pressure increased (53) decreased (48) GFR increased (11,12) decreased (8-10) Proteinuria increased (7) increased (7) Activity of tubular ion transport increased (65,66) decreased (56,59) Tubular mass increased (64) decreased (49) Urine concentrating ability decreased (68, 69) decreased (48) CO = cardiac output; GFR = glomerular filtration rate; RAS = renin-angiotensin system; RBF = renal blood flow.…”

Triiodothyronine enhances renal response to aldosterone in the rabbit collecting tubule.

“…Thus, within 1 wk thyroidectomy induces a marked decrease of the activity and number of catalytic sites of Na-K-ATPase in the proximal and collecting tubules exclusively (1). After administration of a physiologic dose of triiodothyronine to thyroidectomized rabbits, Na-K-ATPase was restored according to a biphasic pattern; an early increase was observed within 3 h, whereas the complete restoration up to control level occurred after 12-24 h (2).…”