Adrenal cortex ascorbic acid

Ascorbic acid depleted in adrenal cortex on stimulation by ACTH Biotin and vitamin A adrenocortical insufficiency noted in biotin and vitamin A deficiency... 

Ascorbic acid adrenal cortex depleted of ascorbic acid on production of aldosterone... 

Ascorbic acid may be required for steroid hormone biosynthesis depleted from adrenal cortex on cortical secretion Biotin adrenocortical insufficiency noted in biotin deficiency... 

Ascorbic acid depleted from adrenal cortex or ovary on progesterone formation Niacin diphosphopyridine nucleotide (DPN) involved in progesterone synthesis... 

In 1933 he synthesized vitamin C (ascorbic acid) and worked on plant glycosides. From 1953 to 1954 he worked with several other scientists and was the first to isolate and explain the constitution of aldosterone, a hormone of the adrenal cortex. He also collaborated with E. C. Kendall and P. S. Hench in their work on the hormones of the adrenal cortex. For this work, Reichstein, Kendall, and Hench were jointly awarded the Nobel Prize for physiology or medicine in 1950. 

Long (1947) soon reported some inconvenient facts from the standpoint of his own provisional hypothesis the injection of ACTH into scorbutic guinea pigs produced the usual fall in adrenal cholesterol (Section XI, 8), together with a lymphopenia, when the ascorbic acid concentration in their adrenal cortices was only 4 per cent of normal. From this it was evident that the cortex can continue to make hormones despite a very low content of ascorbic acid. 

The amount of ascorbic acid in the adrenals is so small in relation to the total amount in the body that even if both glands simultaneously discharged their entire content of ascorbic acid into the blood, the effect on the blood level would be small. This should be kept in mind in interpreting any effects that cortisone or ACTH may have on ascorbic acid in the blood, in terms of immediate events in the cortex they are much more probably reflections of altered oxidation-reduction relationships. 

It is generally assumed today that cholesterol is the raw material from which the adrenal cortex makes its hormones, despite the theoretical doubts of the chemists (see Sayers, 1950). If ascorbic acid were necessary for this synthesis, it might have been expected that scurvy would result in a piling-up of unused cholesterol in the gland, on the analogy of the accumulation of colloid in the thyroid gland deprived of iodine. In fact,... 

An inconvenient fact that needs explanation is that ACTH injected into chicks appears to stimulate the adrenal cortex in the usual manner but produces no change in its ascorbic acid content (Jailer and Boas, 1950). 

Naturally there are obvious objections to this hypothesis for instance, Hechter (1951), in measuring the output of cortical hormones from the perfused adrenals of cows, was unable to find that the presence or absence of ascorbic acid in the perfusion fluid made any difference in the output. He would probably agree, however, that the conditions of his experiment were not precisely physiological, and the results cannot be taken as an indication of what ascorbic acid might be doing within the surviving cells of the cortex. 

Obviously the greatest interest now centers on stress situations. Under some conditions kno to deplete ascorbic acid in the adrenal cortex of animals there is also evidence of an increased catabolism of the vitamin in man. After bums and fractures (Andreae and Browne, 1946) and also in active rheumatoid arthritis (Hall d al., 1939) the level of reduced ascorbic acid in the plasma has been found to be low, requiring unusually large doses to raise it. Apparently the vitamin is used up with abnormal speed in these conditions, thou the mechanism involved is obscure. It is difficult to believe that it is all destroyed in the adrenal cortex under the influence of ACTH discharged from the anterior pituitary, because the amount in the cortex at any one moment is infinitesimal (Section III, 2) compared with the amount that may appear to be lost from the body. According to Sayers et al. (1946), ACTH does not deplete other organs of ascorbic acid, at least in the rat and guinea pig. Perhaps the vitamin is not really destroyed, but merely shifted over to the oxidized form (DHA). 

There are suggestions in the literature that, in addition to ascorbic acid, pteroylglutamic acid, the antipernicious anemia factors, and the adrenal cortex may play a role in tyrosine oxidation in the animal body. The evidence for this is that liver homogenates from rats deficient in pteroylglutamic acid were unable to oxidize tyrosine at a... 

Ascorbic acid has a close relationship to adrenal cortical activity (Chapter 11). Stimulation of the adrenal cortex leads to depletion of ascorbic acid stores in the gland, but even in severe depletion cortical function is maintained. In conditions of stress and after administration of corticotropin, requirement and utilization of ascrobic acid is increased. It has been suggested that ascorbic acid is concerned in the oxidation of a precursor of some adrenal cortical steroid (Chapter 11). Pirani postulated that ascorbic acid may have a nonspecific function related to cellular respiratory activity and metabolic rate. 

The adrenal cortex is very rich in steroids and in ascorbic acid, and is either a factory or a storage depot for these reactants. The metabolic disturbances due to cortical deficiency may be associated with lack of ascorbic acid, and there is evidence that this vitamin is of therapeutic value in the treatment of Addison s disease (Sclare, 1937). The sexual disturbances associated with cortical dysfunction in the female originate probably from abnormal sterol metabolism, as a result of which the tissue either produces an androgen or fails to destroy one. 

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