Aldosterone and thyroid hormone modulation of alpha 1-, beta 1-mRNA, and Na,K-pump sites in rabbit distal colon epithelium. Evidence for a novel mechanism of escape from the effect of hyperaldosteronemia.
Aldosterone and thyroid hormone regulation of Na,K-pump biosynthesis has been examined in the distal colon epithelium of rabbits. Qualitative analysis of alpha-subunit isoform distribution (alpha 1, alpha 2, alpha 3) detected only the alpha 1-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 nM to 1.4-1.9 nM and an increase of alpha 1-mRNA to 162%, beta 1-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 beta 1-mRNA to 55-67%, alpha 1-mRNA to 63-105%, and of [3H]-ouabain binding to 103% of control, suggesting that a reduced rate of synthesis of the beta 1-subunit is rate limiting for Na,K-pump biosynthesis. Substitution with T3 (10 micrograms/kg) at the seventh day with transient restoration of serum T3 to control levels, led to rapid accumulation of beta 1-mRNA to 152%, of alpha 1-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.(ABSTRACT TRUNCATED AT 250 WORDS)
August Krogh Institute, Copenhagen University, Denmark.
H
H
Wiener
J M
JM
Nielsen
D A
DA
Klaerke
P L
PL
Jørgensen
D000450:Aldosterone / Q000097:blood / Q000502:physiology*; D000818:Animals; D015152:Blotting, Northern; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002846:Chromatography, Affinity; D003106:Colon / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D004039:Diet, Sodium-Restricted; D015536:Down-Regulation; D004847:Epithelial Cells; D004848:Epithelium / Q000737:chemistry / Q000502:physiology; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006929:Hyperaldosteronism / Q000097:blood / Q000503:physiopathology*; D007536:Isomerism; D010042:Ouabain / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D011817:Rabbits; D012964:Sodium / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013974:Thyroxine / Q000097:blood / Q000502:physiology*; D014284:Triiodothyronine / Q000097:blood / Q000502:physiology*; D014316:Tritium
D012333:RNA, Messenger; D014284:Triiodothyronine; D014316:Tritium; D000450:Aldosterone; D010042:Ouabain; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D013974:Thyroxine