1. The effect of the administration of oestrone sulphate on tryptophan metabolism has been assessed in rats in order to determine whether and to what extent inhibition of tryptophan metabolism by oestrogens may be a factor in the aetiology of pellagra, and might explain the reported twofold excess of females over males in many outbreaks of pellagra.2. Feeding ovariectomized rats for 1 week on a diet containing 15 mg oestrone sulphate/kg led to significant inhibition of kynurenine hydroxylase (EC 1 .14.13.9), kynureninase (EC 3 . 7 . 1 .3) and 3-hydroxyanthranilate oxidase (EC 1 . 13.11 .6). There was also a significant increase in plasma tryptophan, suggesting decreased activity of tryptophan oxygenase (EC 1 .13. 11 . 11). This inhibition of tryptophan metabolism will result in a considerable reduction in the synthesis of the nicotinamide nucleotide coenzymes (NAD and NADP) from tryptophan.3. When ovariectomized rats were maintained for 4 weeks on a diet providing no preformed niacin and only a marginally adequate amount of tryptophan (1030 mg/kg), the addition of oestrone sulphate to the diet led to a significant reduction in the liver content of nicotinamide nucleotides and the urinary excretion of the end-product of NAD metabolism, W-methyl nicotinamide.4. It is suggested that when the diet is only marginally adequate in tryptophan and niacin, inhibition of tryptophan metabolism by endogenous or administered oestrogens may be an additional factor in the development of pellagra.Miller (1978) drew attention to the fact that during the first half of the present century, when pellagra was a major problem of public health nutrition in the United States, there was an approximately twofold excess of females over males in the reported deaths from the disease. Over the four decades from 1920 to 1960 a total of 59391 deaths of women were attributed to pellagra, compared with 28022 deaths of males.Individual reports of outbreaks of pellagra also show an excess of females over males. In the 'epidemic' of pellagra at the Mount Vernon Insane Hospital in Alabama in 1906, only eight of a total of eighty-eight cases were men (Searcy, 1907). Albright (1912) reported on 3 16 cases of pellagra in Tennessee; 2 14 were females and 102 males. Aykroyd et al. (1 935) reported that in four Rumanian villages 79% of pellagra victims were females, and in outbreaks of the disease in Missouri and in Georgia in the USSR 72-73 % of the pellagrins were female. More recently there has been a resurgence of pellagra in Zaire (Ermolieff & Grosshans, 1979); in this outbreak there was no difference between the numbers of females and males under the age of 16 years, but in the range of 18-32 years of age there was a small excess of females over males (forty-six women compared with thirty-nine men). Unfortunately, there is no epidemiological information in Casal's original report of la ma1 de la rosa. He described eleven cases in some detail; six were women and five men (Gonzalez, 1900).A number of factors, especially cultural ones, may be responsi...
Acute administration of vitamin B6 to rats (10 mg/kg body weight) led to reduced urinary excretion of N1-methyl nicotinamide and methyl pyridone carboxamide, indicating inhibition of the oxidative metabolism of tryptophan. There was a considerable reduction in the production of 14CO2 from [ring-2-14C]tryptophan, and a significant inhibition of hepatic tryptophan oxygenase when measured in liver homogenates, together with an increase in the concentration of tryptophan in plasma. There was an increase in both the concentration of tryptophan in the brain and the uptake into the brain of peripherally administered [3H]tryptophan, accompanied by a small increase in the rate of synthesis of 5-hydroxytryptamine in the brain. It is suggested that this increase in the uptake of tryptophan into the brain following a relatively large dose of vitamin B6 may explain the beneficial action of the vitamin in some cases of depressive illness.
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