Cellular Mechanism of Aldosterone Action

Cellular Mechanism of Aldosterone Action

Although for many years we have known the overall effects of mineralocorticoids on the body, the basic action of aldosterone on the tubular cells to increase transport of sodium is still not fully understood. However, the cellular sequence of events that leads to increased sodium reabsorption seems to be the following.

First, because of its lipid solubility in the cellular membranes, aldosterone diffuses readily to the interior of the tubular epithelial cells.

Second, in the cytoplasm of the tubular cells, aldos-terone combines with a highly specific cytoplasmic receptor protein, a protein that has a stereomolecularconfiguration that allows only aldosterone or very similar compounds to combine with it.

Third, the aldosterone-receptor complex or a product of this complex diffuses into the nucleus, where it may undergo further alterations, finally induc-ing one or more specific portions of the DNA to form one or more types of messenger RNA related to the process of sodium and potassium transport.

Fourth, the messenger RNA diffuses back into the cytoplasm, where, operating in conjunction with the ribosomes, it causes protein formation. The proteins formed are a mixture of (1) one or more enzymes and (2) membrane transport proteins that, all acting together, are required for sodium, potassium, and hydrogen transport through the cell membrane. One of the enzymes especially increased is sodium-potassium adenosine triphosphatase, which serves asthe principal part of the pump for sodium and potas-sium exchange at the basolateral membranes of the renal tubular cells. Additional proteins, perhaps equally important, are epithelial sodium channel pro-teins inserted into the luminal membrane of the same tubular cells that allows rapid diffusion of sodium ions from the tubular lumen into the cell; then the sodium is pumped the rest of the way by the sodium-potassium pump located in the basolateral membranes of the cell.

Thus, aldosterone does not have an immediate effect on sodium transport; rather, this effect must await the sequence of events that leads to the formation of the specific intracellular substances required for sodium transport. About 30 minutes is required before new RNA appears in the cells, and about 45 minutes is required before the rate of sodium transport begins to increase; the effect reaches maximum only after several hours.