The investigative work presented in this thesis is a contribution to the great amount of knowledge that already exists in the field of sodium and potassium metabolism. The study has been done on rats, but differs from earlier work in the method used. The experimental approach combines previously described techniques, modified for the purpose, and new procedures created for special needs. [...]

The regulation of water and electrolyte metabolism has been the subject of much investigation. Many factors have been implicated, one being that volume plays a role in the regulation of sodium in the body. It has been suggested that there may be receptors somewhere in the body, which are sensitive to changes in the volume of fluid or in the concentration of electrolytes. It has not been clearly established yet whether they are sensitive to blood volume, plasma colloid osmotic pressure, interstitial fluid volume, or some other factor. The importance of the adrenal cortex in influencing sodium metabolism is well established.

Almost forty years have elapsed since the discovery of insulin by banting and best, but its mechanism of action is still far from being completely elucidated. Although the number of relevant publications is steadily increasing, up to the present date no unanimity of scientific opinion exists as to the site of insulin action. Two opposing concepts emerged as a result of investigations. One group of workers considered that the main factor in causing hypoglycemia is the effect of insulin to increase the rate of glucose utilization another school of thought attributed the blood sugar lowering action of insulin to an almost complete cessation of hepatic glucose output.

Replacement therapy provided the first element of knowledge of the nature of adrenocortical secretion. The earliest view on this secretion assumed the existence of a single adrenocortical hormone, called "cortin" (5}. Attempts were made to extract, isolate and characterize this principle from the adrenals. ROGOFF et al. round that aqueous extracts of adrenal tissue have the property of maintaining life in adrenaleotomized animals. ( 6) SWINGLE et al. in 1931 (7) demonstrated unequivocally that the fraction soluble in usual lipid solvents possesses a far greater potency.

The nephrotic syndrome is most frequently encountered in children within the age group of one to six years. It is characterized by the occurrence of massive albuminuria, hypoproteinemia, hyperlipemia and voluminous edema. When this syndrome is almost pure, that is to say, when it is not accompanied by hematuria, renal insufficiency or hypertension, it has for a long time been referred to as lipuid nephrosis. The German anatomists (MUNK, 1908; VOLLARD AND FAHR 1913) were the first to use this name arising from the observation that the renal tubules are infiltrated by birefringent liquid substances accompanied by signs of inflammation.

In recent years after Grundy, Simpson and Tait (73) discovered aldosterone in beef adrenal extract, the attention was drawn to this hormone. Because of the importance of aldosterone in regulation of the electrolyte balance in the organism, a number of investigations were done to elucidate the factors involved in the control of aldosterone secretion. The conducted experiments showed, that aldosterone elaboration was not completely dependant on the ACTH. [...]

The numerous observations of increased levels of blood and urinary 17-hydroxycorticosteroids in human pregnancy associated with a rising output of 17-ketosteroids and aldosterone have suggested to many investigators that adrenal cortical function is increased in this condition. In some pregnant women with adrenal insufficiency increased urinary corticosteroids and 17-ketosteroids have also been reported and the possibility that the placenta may be elaborating corticosteroids has frequently been suggested.

The capacity of both the human liver and hepatic tissue from various animal species to synthesize, interconvert and destroy many, if not all, of the large number of estrogens now known to exist, has been amply demonstrated by numerous workers. Techniques have so changed and improved in the past decade that it is now possible to have definitive and quantitative concepts about the different reaction sequences. It is fully realized that these same advances present grave difficulties (such as the determination of radiochemical purity) which will be discussed later in this work.

Interest was aroused in thyroid immunology and its relationship to thyroid pathology by the recent publications of two groups of investigators. Witebsky, Rose and Shullman, a team of immunologists working on organ-specificity of the thyroid gland were successful in immunizing rabbits with their own thyroid extract, and, they also demonstrated morphologic changes in the thyroid gland which resembled those seen in Hashimoto's disease. Doniach, Roit and Hudson, a group of clinical investigators demonstrated the presence of thyroid auto-antibodies in the sera of patients with Hashimoto's disease.

That the energy requirements for muscular exercise in the human organism are derived largely from the oxidative metabolism of carbohydrate in the working muscles has been known for many years (43). The chain of biochemical reactions within the muscle fibre which result in fibre contraction are known in intimate detail as are the neuro-humoral mechanisms controlling and coordinating fibre contraction in the individual fibre groups and muscle bundles . Concerning the physiological mechanisms controlling the participation of the respiratory apparatus, the heart and the blood vessels in increasing the supply of oxygen to the working muscles, there is little knowledge and much speculation.