TY - JOUR

T1 - Aldosterone and thyroid hormone modulation of α1-, β1-mRNA, and Na,K-Pump sites in rabbit distal colon epithelium. Evidence for a novel mechanism of escape from the effect of hyperaldosteronemia

AU - Wiener, Hubert

AU - Nielsen, Jesper M.

AU - Klaerke, Dan A.

AU - Jørgensen, Peter L.

PY - 1993/5

Y1 - 1993/5

N2 - Aldosterone and thyroid hormone regulation of Na,K-pump biosynthesis has been examined in the distal colon epithelium of rabbits. Qualitative analysis of α-subunit isoform distribution (α1, α2, α3) detected only the α1-mRNA in the distal colon epithelium and outer renal medulla, while all three isoforms were observed in rabbit brain. A low-sodium diet led to a rise in serum aldosterone from 0.6 n m to 1.4-1.9 n m and an increase of α1-mRNA to 162%, β1-mRNA to 120%, and the number of Na,K-pump units as determined by specific [3H]-ouabain binding to 182% of control by the second day of the diet. While aldosterone levels remained elevated, a spontaneous decrease in serum levels of T3 and T4 to 50-60% of control from the third day of the diet was followed by downregulation of β1-mRNA to 55-67%, α1-mRNA to 63-105%, and of [3H]-ouabain binding to 103% of control, suggesting that a reduced rate of synthesis of the β1-subunit is rate limiting for Na,K-pump biosynthesis. Substitution with T3 (10 μg/kg) at the seventh day with transient restoration of serum T3 to control levels, led to rapid accumulation of β1-mRNA to 152%, of α1-mRNA to 135%, and of the number of Na,K-pump units to 153% of control. This is consistent with thyroid hormone having a permissive role for the aldosterone stimulation of Na,K-pump biosynthesis. Reduced rates of β-subunit transcription due to low thyroid hormone levels appear to provide a mechanism for escape from the effect of hyperaldosteronemia on the number of Na,K-pump units.

AB - Aldosterone and thyroid hormone regulation of Na,K-pump biosynthesis has been examined in the distal colon epithelium of rabbits. Qualitative analysis of α-subunit isoform distribution (α1, α2, α3) detected only the α1-mRNA in the distal colon epithelium and outer renal medulla, while all three isoforms were observed in rabbit brain. A low-sodium diet led to a rise in serum aldosterone from 0.6 n m to 1.4-1.9 n m and an increase of α1-mRNA to 162%, β1-mRNA to 120%, and the number of Na,K-pump units as determined by specific [3H]-ouabain binding to 182% of control by the second day of the diet. While aldosterone levels remained elevated, a spontaneous decrease in serum levels of T3 and T4 to 50-60% of control from the third day of the diet was followed by downregulation of β1-mRNA to 55-67%, α1-mRNA to 63-105%, and of [3H]-ouabain binding to 103% of control, suggesting that a reduced rate of synthesis of the β1-subunit is rate limiting for Na,K-pump biosynthesis. Substitution with T3 (10 μg/kg) at the seventh day with transient restoration of serum T3 to control levels, led to rapid accumulation of β1-mRNA to 152%, of α1-mRNA to 135%, and of the number of Na,K-pump units to 153% of control. This is consistent with thyroid hormone having a permissive role for the aldosterone stimulation of Na,K-pump biosynthesis. Reduced rates of β-subunit transcription due to low thyroid hormone levels appear to provide a mechanism for escape from the effect of hyperaldosteronemia on the number of Na,K-pump units.

KW - aldosterone

KW - distal colon epithelium

KW - Na,K-ATPase

KW - sodium pump

KW - thyroid hormone

UR - http://www.scopus.com/inward/record.url?scp=0027319448&partnerID=8YFLogxK

U2 - 10.1007/BF00232020

DO - 10.1007/BF00232020

M3 - Journal article

C2 - 8392583

AN - SCOPUS:0027319448

VL - 133

SP - 203

EP - 211

JO - Journal of Membrane Biology

JF - Journal of Membrane Biology

SN - 0022-2631

IS - 3

ER -