Cellular Mechanism of Aldosterone
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
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.