J Exp Med 1961 Sep 30;1144:581-92.

CHANGES IN CONNECTIVE TISSUE AND INTESTINE CAUSED BY VITAMIN A IN AMPHIBIA, AND THEIR ACCELERATION BY HYDROCORTISONE.

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In view of the theory that an excess of vitamin A causes release of cathepsins from intracellular lysosomes, hypervitaminosis A was induced orally in the larvae of Xenopus laevis. It was predicted that the tails of these amphibia would undergo resorption prior to metamorphosis, since the presence of abundant lysosomes, associated with measurable increases of catheptic activity, had previously been demonstrated in the resorbing tails of amphibia during metamorphosis. This prediction was confirmed; after 3 to 4 weeks of hypervitaminosis A, the tails of treated animals underwent partial resorption. Other transitory appendages, the rostral tentacles, collapsed after 2 weeks of treatment with an excess of vitamin A, an effect analogous to the collapse of rabbits' ears after intravenous papain. These effects were related to the loss of metachromatic extracellular material in these appendages. Excess of vitamin A caused kyphoscoliosis and prognathos in the larvae. The hypervitaminotic larvae always developed a mucinous diarrhea, which was associated with a remarkable overgrowth of metachromatic goblet cells of the intestine. The entire intestine of the treated animals was more advanced in development than that of control larvae at equivalent stages. All the effects of hypervitaminosis A were accelerated by the simultaneous administration of hydrocortisone. This was held to be due to liberation of vitamin A from hepatic stores by the steroid, and is in contrast to the retardation of hypervitaminosis A by hydrocortisone in vitro.

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