Edward C. Kendall

The Influence of the Adrenal Cortex on the Metabolism of Water and Electrolytes

Publisher Summary This chapter discusses the influence of the adrenal cortex on the metabolism of water and electrolytes. The nature of the changes produced by adrenalectomy on the metabolism of sodium, potassium, and chloride and the influence of the adrenal cortex on physiologic processes are examined. The metabolism of sodium, potassium, and chloride is in large measure controlled by the hormones of the adrenal cortex. The physiologic response to administration of the hormones of the adrenal cortex is in large measure determined by the amount of sodium and chloride present in the body. The adrenal cortex furnishes a mechanism to the body, which modifies the transfer of sodium, potassium, and chloride through cellular structures. In a normal animal deprived of salt, the transfer of sodium and chloride from the glomerular filtrate to the blood against osmotic pressure until almost no sodium or chloride remains in the urine is perhaps the best example of the essential action of the adrenal cortex. The remarkable effect of sodium chloride on renal function depends on something more than restoration of blood volume and of the normal concentration of electrolytes.

Influence of Amorphous Fraction from Adrenal Cortex on Efficiency of Muscle

An extract of the atlrenal cortex which is free from epinephrine and contains the physiologically active steroid derivatives characteristic of the adrenal cortex can he separated into a surprisillgly large number of crystalline compounds and an amorphous fraction. The crystalline compounds A, B, E, and F, which have an atom of oxygen attached to C11, have a nlarked effect on the efficiency of muscle 1 and on carbhidrate metabolism 2 3 , hut relatively large amotmts are recluired to maintain renal function. When large amounts are administered to normal male rats these compounds produce atrophy of the adreiial and thymus glands. 4 , 5 Desoxycorticosterone, which is identical with compound B except that there is no atom of oxygen on C11, has hut little effect on the efficiency of muscle and on carbohydrate metabolism, hut it is from 6 to 10 times more efficient than compound E when renal function is used as a criterion. The amorphous fraction has the greatest effect on renal function aid it protects the adrenalectomized animal against certain forms of stress such as a low environmental temperature, but even 40 times the amount of this fraction which is required to produce these effects does not cause atrophy of the thymus or adrenal glands. It has also heen shown that the amorphous fraction has very little effect on carhohydrate metabolism. 6 It became desirable, therefore, to determine whether this fraction could increase the eficiency of muscle to a degree comparable to compounds A, B, E, and F. In the present report it will be shown that very small amounts of the amorphous fraction will protect the adrenalectomized rat against a loss in body weight, but that animals so treated are incapable of sustained work.

A New Iodine Compound for Cholecystography

THE extensive use of sodium tetrabromphenolphthalein and sodium tetraiodophenolphthalein in cholecystography, since they were first introduced by Graham and his associates, has shown that these two compounds will serve efficiently. Intravenous administration of these drugs for cholecystography has the advantage of assuring that a specified dose has been introduced into the circulation, and thus obviates all question concerning absorption through the intestinal wall. Menees and Robinson, in 1925, showed that the bromine salt could be given effectively by mouth, and shortly afterward Whitaker began to administer the iodine salt orally. The oral method is generally deemed safer from severe reactions, more facile of application, and hence more practicable. This is especially true where large numbers of patients are to be examined daily. Excellent results have been obtained at the Mayo Clinic through the oral use of the sodium salt of tetrabromphenolphthalein. However, the occasional reactions from the oral me...

Oxidation of Cobaltous Cysteine.

Michaelis and Barron 1 and Michaelis and Yamaguchi 2 have shown that cobalt reacts with cysteine to form a product which has a high reduction intensity. They also showed that this reaction product can be oxidized with air, ferri-cyanide, and phenolindophenol to a brown cobaltic cysteine complex. We have found that cobaltous cysteine reacts in a different manner toward each one of these oxidants. Indigo disulfonate produces a quantitative conversion of cobaltous cysteine to the cobaltic cysteine complex. All other oxidants except those which contain a quinone group result in the formation of the cobaltic cysteine complex and cystine in different proportions. Oxidation with ferricyanide produces a unique type of electrometric titration curve because all of the cobaltous cysteine is removed from solution by addition of a half of the total amount of oxidant. The last half of the curve represents oxidation of cysteine to cystine. Cysteine reacts with quinone and with the quinone group of dibromophenol-indophenol with the formation of an addition product between the dye and the thiol group similar to the addition of an aromatic thiol group to quinone. One molecule of cysteine reacts with 1 molecule, that is, 2 equivalents of the dye. Ninety per cent of cobaltous cysteine is oxidized to the cobaltic cysteine complex with dibromophenolindophenol, and 10% of the cysteine combines with the dye. The amounts of cobaltic complex and cystine formed by each oxidant are such that the amounts of ferricyanide, oxygen, and indophenol required for a given amount of cysteine are all equal to two-thirds the amount of the cysteine.

Response to acceptance of the Scientific Achievement Award.

The late Dr. Charles Mayo used to say that if someone wanted to give him flowers he hoped that they would do so while he could smell them. It is an honor to accept the Scientific Achievement Award and it is a pleasure to receive it while I can stand on my feet. My response will concern some observations about time and some conclusions which have been reached during the past 55 years, all of which have been spent in a chemical laboratory. The passing years have been compared with the flight of an arrow. Time does not change its course, and any research problem either is carried forward or it slips from its place in the procession. Prior to 1492 the Western Hemisphere was visited by more than one explorer, but the old world was not ready to expand. The reports of these explorers soon were forgotten. Superstition, fear,

Study of Reversible Oxidation of Adrenaline and Its Derivatives.

Ephedrine, adrenalone, methylacetopyrocateehol, dimethylacetopyrocatechol, adrenaline, the ethyl and methyl ethers and the anhydride of adrenaline were investigated to see whether (a) they would be oxidized by dibromophenolindophenol, naphtholidichloroindophenol, methylene blue and indigo carmine; (b) whether the oxidized forms would act as oxidizing agents with reduced indigo; (c) whether they formed reversible oxidation-reduction systems; (d) whether under any conditions they would function as cyclic cataclysts. All of the eight substances, except ephedrine, are oxidized by dibromophenolindophenol. Adrenaline and its ether derivatives are oxidized by only the last mentioned oxidizing dye. Adrenalone, methylacteopyrocatechol, and dimethylacetopyrocatechol are oxidized by naphtholdichloroindophenol and indigo carmine. Adrenalone and methylaminoacetopyrocatechol are oxidized by all of the dyes. Dimethylacetopyrocatechol is not oxidized by methylene blue, but is oxidized by indigo carmine. These results emphasize the fact that the configuration of the oxidizing dyes is of greater importance than the intensity of oxidation produced by the dye. Adrenalone, methyl and dimethylacetopyrocatechol will oxidize reduced indigo after they have been oxidized with the dyes. The oxidation is quantitatively reversible. Adrenaline and its ethers cannot be reversibly oxidized. The probable point of attack of the oxidizing agent in all of these compounds is the two hydroxyl groups on the benzene ring, with the formation of an ortho-quinone. This derivative of adrenalone can be reduced, but, with adrenaline some other part of the molecule absorbs the oxidizing power of the ortho-quinone, resulting in an irreversible reaction. At a pH of 7.4 and in the presence of a third component, adrenaline will act as a cyclic catalyst bringing about the oxidation of adrenaline with molecular oxygen. The essential configuration of the third component has not been determined, but it is prepared by the action of sodium hydroxide on glucose.