Scurvy hormones

Sato P and Udenfriend S (1978) Studies on ascorbic acid related to the genetic basis of scurvy. Vitamins and Hormones 36,33-52. 

Another method that has been used to measure the excretion of adrenal steroids is the determination of formaldehydogenic steroids in the urine. This is no longer considered a reliable method of chemical assay and bears no certain relation to adrenocortical function (Marrian, 1952) nevertheless, it is worth reviewing the results obtained by this method in human scurvy. When ascorbic acid was administered to three patients with scurvy, instead of the expected increase in the excretion of formalde-hydogenic hormones, there was a fall in their excretion lasting several days (Daughaday et al., 1948). 

Even the most ardent supporters of the belief that ascorbic acid is concerned in the synthesis of cortical hormones would probably hesitate today to suggest that this is the most important function of ascorbic acid in the body, still less its only function there are too many obvious reasons for thinking otherwise. The first is that human patients whose adrenals have been destroyed suffer from Addison s disease but do not develop scurvy. They continue to show normal levels of ascorbic acid in the blood (Jenovese el al., 1940), and there is no evidence that their collagen is affected. Though there were some initial reports (e.g., Wilkinson and Ashford, 1936) that patients with Addison s disease suffered from ascorbic acid deficiency, this idea has faded from the recent literature. Secondly, the amount of ascorbic acid in the adrenal cortices is less than 1 per cent of the total amount in the human body (Section III, 2) it would be against what we know of the economy of the body to think that all the rest of this active metabolite was simply hanging around in the other tissues, waiting for the adrenals to find a use for it. 

It is worth-while nevertheless to consider what may happen in experimental scurvy when the adrenal cortex is (a) relieved of its task of making hormones by directly injecting them, and (b) stimulated to greater hormonal output. This is considered in the following section. Many of the facts have already been reviewed by Morgan (1951). 

It is concluded that injections of cortisone and ACTH fail to produce the specific effects in scurvy that should have been expected if ascorbic acid were essential for the formation and secretion of cortical hormones. 

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,... 

In summation, it seems fair to say that to date there is no undisputed evidence that ascorbic acid plays any part in assisting the synthesis or secretion of the adrenocortical hormones. As Long himself has shown (1947) the scorbutic guinea pig appears to respond quite normally to ACTH. There is no evidence of cortical failure in human scurvy. Injec-... 

In the last year or two there has been a tendency to assume that whereas the normal healthy cortex regularly uses ascorbic acid for the synthesis of its hormones, it can, at a pinch (e.g., in scurvy) get on without it—probably by using something else in its place (e.g., glutathione). This is a striking example of the unscientific method at work the tailoring of the facts to fit an established theory. In the writer s opinion the present facts require a fresh hypothesis. 

Ascorbate and Hormone Balance. The highest concentrations of ascorbate are found in the adrenal and pituitary glands, and the terminal stages of scurvy are just preceded by complete depletion of adrenal ascorbate, leading, it has been frequently stated, to scurvy death from adrenocortical failure. This has caused many to suggest that the ascorbic acid-dehydroascorbic acid system plays an important role in the synthesis and release of hormones of the adrenopituitary axis. The evidence for this is both conflicting and confusing (13, 72, 73,102, 277, 278). 

In conclusion, in spite of the simplicity of the structure of the molecules, the exact role that ascorbic acid plays as a coenzyme remains unknown. The vitamin is suspected to influence reactions in numerous metabolic pathways (see Fig. 4-19), and it also interacts in some way with hormones. Whether the role of ascorbic acid is a specific one as a coenzyme or results from its potent reductive properties is not clear. In any case, the metabolic alteration which seems to be most closely related to the clinical manifestation of scurvy is the conversion of proline to hydroxyproline. 

Rajalakshmi et al (1967) confirmed the synthesis of AA in human placenta Earlier, Bagchi (1952) had reported the absence of scurvy during pregnancy and lactation in poor Ihdian women Unlike plants, the storage, distribution and synthesis of AA in rats and cockerals are regulated by hormones (Dieter, 1969 Majumder and Chatterjee, 1974 Chinoy, N J and Seethalakshmi, 1978 Chinoy, N J and Rao, 1979 ... 

---