Maturation of the Na+/H+ antiporter (NHE3) in the proximal tubule of the hypothyroid adrenalectomized rat.
In previous studies examining the role of glucocorticoids and thyroid hormone on the maturation of the Na(+)/H(+) antiporter (NHE3), we found attenuation in the maturational increase in proximal tubule apical Na(+)/H(+) antiporter activity but no change in NHE3 mRNA abundance in either glucocorticoid-deficient or hypothyroid rats. In addition, prevention of the maturational increase in either hormone failed to totally prevent the maturational increase in Na(+)/H(+) antiporter activity. We hypothesized that one hormone played a compensatory role when the other was deficient. The present study examined whether combined deficiency of thyroid and glucocorticoid hormones would completely prevent the maturation of the Na(+)/H(+) antiporter. Adrenalectomy was performed in 9-day-old hypothyroid Sprague-Dawley rats, a time before the normal postnatal maturational increase in these hormones occurs. Nine- and 30-day-old adrenalectomized (ADX), hypothyroid rats had comparable NHE3 mRNA abundance, which was 5- to 10-fold less than 30-day-old ADX, hypothyroid rats that received corticosterone-thyroxine replacement and 30-day-old sham control rats (P < 0.05). Brush-border membrane NHE3 protein abundance was comparable in 9- and 30-day-old ADX, hypothyroid groups and approximately 20-fold lower than both the 30-day replacement and 30-day sham groups (P < 0.05). Similarly, the replacement and sham groups had higher sodium-dependent proton secretion than 9- and 30-day-old ADX, hypothyroid groups (P < 0.05). We conclude that combined deficiency of both hormones totally prevents the maturational increase in NHE3 mRNA and protein abundance and Na(+)/H(+) antiporter activity.
Gupta
Neena
N
Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9063, USA.
Dwarakanath
Vangipuram
V
Baum
Michel
M
D000315:Adrenalectomy; D000818:Animals; D000831:Animals, Newborn; D001639:Bicarbonates / Q000097:blood; D001835:Body Weight; D003345:Corticosterone / Q000097:blood / Q000172:deficiency; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007037:Hypothyroidism / Q000378:metabolism* / Q000503:physiopathology; D007687:Kidney Tubules, Proximal / Q000254:growth & development* / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics* / Q000378:metabolism*; D013963:Thyroid Hormones / Q000494:pharmacology; D013974:Thyroxine / Q000097:blood / Q000172:deficiency
D001639:Bicarbonates; D005938:Glucocorticoids; D012333:RNA, Messenger; C000613387:Slc9a3 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D013963:Thyroid Hormones; D013974:Thyroxine; D003345:Corticosterone