Effects
Progesterone exerts its primary action through the intracellular progesterone receptor although a distinct, membrane bound progesterone receptor has also been postulated. In addition, progesterone is a highly potent antagonist of the mineralocorticoid receptor (MR, the receptor for aldosterone and other mineralocorticosteroids). It prevents MR activation by binding to this receptor with an affinity exceeding even those of aldosterone and other corticosteroids such as cortisol and corticosterone.
Progesterone has a number of physiological effects that are amplified in the presence of estrogen. Estrogen through estrogen receptors upregulates the expression of progesterone receptors. Also, elevated levels of progesterone potently reduce the sodium-retaining activity of aldosterone, resulting in natriuresis and a reduction in extracellular fluid volume. Progesterone withdrawal, on the other hand, is associated with a temporary increase in sodium retention (reduced natriuresis, with an increase in extracellular fluid volume) due to the compensatory increase in aldosterone production, which combats the blockade of the mineralocorticoid receptor by the previously elevated level of progesterone.
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