Mineralocorticoids, function

The adrenal glands are sensitive to the toxic effects of suramin both glucocorticoid and mineralocorticoid functions can be impaired at doses normally used, necessitating replacement therapy (1081). 

Mineralocorticoid function. Sodium, potassium, and chloride determinations were made. Sodium levels were found to be low in 8 of 29 cases chloride levels were low in 16 of 43 cases and potassium levels were high in 7 of 27 cases. Although the number of observations was small, the results suggest that at least in some cases lowered mineralocorticoid function may be a factor, and that a further study of this point would be of interest. Electrolyte changes of this sort were reported by Keys et al (1950). 

Steroid Hormones and Neurosteroids. Steroids (qv) can affect neuroendocrine function, stress responses, and behavioral sexual dimorphism (78,79) (see Steroids). Mineralocorticoid, glucocorticoid, androgen, estrogen, and progesterone receptors are localized in the brain and spinal cord. In addition to genomic actions, the neurosteroid can act more acutely to modulate the actions of other receptors or ion channels (80). Pregnenolone [145-13-17, ( ) dehydroepiandosterone [53-43-0] C H2 02 (319) are excitatory neurosteroids found in rat brain, independent of adrenal... 

Several diseases involving dysregulation of MR function have been described although most of them are not causatively linked to the receptor itself. Pseudohypoaldosteronism for example is a syndrome of mineralocorticoid resistance characterized by urinary salt loss and dehydration. However, only very rarely mutations in the MR gene have been found in these patients so far. In most cases, this syndrome appears to be linked to defects in the subunits of the amiloride-sensitive sodium channel ENaC, a major target of mineralocorticoid action in the kidney. 

The answer is c. (Hardmanr pp 706-708.) Spironolactone is an aldosterone antagonist that acts on the mineralocorticoid receptor It is a Kksparing diuretic. It can also function as an androgen antagonist, which could explain the gynecomastia and erectile dysfunction. Women with hirsutism are sometimes treated with spironolactone. 

Arriza, J. L., Weinberger, C., Cerelli, G. et al. Cloning of the human mineralocorticoid receptor complementary DNA Structural and functional kinship with the glucocorticoid receptor. Science 237 268-275,1987. 

In particular, it should be noted that since 11-deoxycorticosterone does not exhibit glucocorticoid activity yet, it is a powerful mineralocorticoid and has only two potentially reactive substituents capable of reacting with a receptor, and the interaction should occur by way of a Cj-keto and/or a Ci7j3-C0-CH20H groups. The necessity of either a simultaneous presence of acidic functions at Cu and or the necessity of simultaneous absence of acidic functions at and C17 in the structure of the pregnane system is also apparent. 

Another major function of the adrenal cortex is the regulation of water and electrolyte metabolism. The principal mineralocorticoid, aldosterone, can increase the rate of sodium reabsorption and potassium excretion severalfold. This will occur physiologically in response to sodium or volume depletion or both. The primary site of... 

Trapp T, Holsboer F Heterodimerization between mineralocorticoid and glucocorticoid receptor increases the functional diversity of corticosteroid action. Trends Pharmacol Sci 17 145-149, 1996... 

J. L. Arriza, C. Weinberger, G. Cerelli, T. M. Glaser, B. L. Handelin, D. E. Housman, R. E. Evans (1987). Cloning of human mineralocorticoid receptor c-DNA structural and functional kinship with the glucocorticoid receptor. Science 227 268-275. 

When given in larger than physiologic amounts, steroids such as cortisone and hydrocortisone, which have mineralocorticoid effects in addition to glucocorticoid effects, cause some sodium and fluid retention and loss of potassium. In patients with normal cardiovascular and renal function, this leads to a hypokalemic, hypochloremic alkalosis and eventually to a rise in blood pressure. In patients with hypoproteinemia, renal disease, or liver disease, edema may also occur. In patients with heart disease, even small degrees of sodium retention may lead to heart failure. These effects can be minimized by using synthetic non-salt-retaining steroids, sodium restriction, and judicious amounts of potassium supplements. 

A form of salt loss in infancy was long considered to be due to renal tubules that were refractory to aldosterone. Recent studies have described variant roots of the condition, either mutations in the mineralocorticoid receptor, the genes coding the epithelial sodium channel (ENaC), or other causes [6]. Many infant patients recover spontaneously, probably due to maturation of proximal tubular function. 

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