Adaptation of the mineralocorticoid target tissues to the high circulating cortisol and progesterone plasma levels in the squirrel monkey

Many New World primate species have elevated circulating free plasma cortisol concentrations, target tissue resistance to cortisol, and no evidence of sodium retention. A representative New World primate, the squirrel monkey (Saimiri sciureus), has plasma cortisol concentrations above those necessary to cause complete suppression of the renin-angiotensinaldosterone axis in an Old World primate, the cynomolgus monkey (Macaca fascicularis). Despite this, the arterial blood pressure as well as the plasma sodium, potassium, and bicarbonate levels of the squirrel monkey are similar to those of the cynomolgus monkey, and its plasma aldosterone concentrations are approximately 2-fold higher. These findings suggest that cortisol has minimal sodium-retaining effects in this species. Renal cytosol aldosterone receptor concentrations are about 2- to 3-fold lower in the squirrel monkey than in the cynomolgus, whereas the receptor affinities for [³H] aldosterone are similar in the two monkeys. Higher concentrations of cortisol are needed to displace [³H]aldosterone from the mineralocorticoid receptor in the squirrrel monkey than from the renal receptor in the cynomolgus [apparent equilibrium dissociation constant (K₁) = 7.8 × 10^-7 vs. 2.9 × 10^-8 M, respectively]. In addition, in contrast to man and presumably other Old World primates, plasma aldosterone concentrations in the female squirrel monkey do not increase during the reproductive cycle or pregnancy when progesterone concentrations are 10- to 20-fold higher than those of the male or the reproductively quiescent female. This suggests that progesterone is a poor aldosterone antagonist in this species. We conclude that a low concentration of mineralocorticoid receptors in New World Primates is compensated for by higher aldosterone levels, with a concomitant increase in receptor occupancy. The salt-retaining potency of cortisol is low, presumably because of a decrease in the affinity of the aldosterone receptor for glucocorticoids in New World primates.