1. A study has been made of epithelial transformations in the male genital tract of estrogentreated mice, rats, guinea pigs, and rabbits; of avitaminotic-A mice and rats; of methylcholanthrene-treated rats; and of rabbits with spontaneous metaplastic lesions.

  2. Comparison of metaplastic alterations in mice and rats after estrogen treatment and with vitamin A deficiency reveals three possible histologic distinctions: (a) consistently “centripetal” growth of replacing epithelium in the former compared with secondarily “centrifugal” growth in the latter; (b) the occurrence of proliferation of alkaline phosphatase-positive basal cells in the former; and (c) the considerably more extensive occurrence of keratinizing stratified squamous epithelium in the latter. Histologic similarity of the metaplastic transformations in the two syndromes may be only superficial.

  3. The possible utility of the Barger-Gomori histochemical technic for alkaline phosphatase in distinguishing estrogen-induced metaplasia from neoplastic transformations is suggested.

  4. The role of alkaline phosphatase activity in estrogen-induced metaplasia is considered. Possibly it is an indicator of cytoplasmic metabolic activity accompanying non-neoplastic cell proliferation. A constant relation between such activity and keratin synthesis is not supported.

  5. The mechanisms of metaplastic transformations require further investigation, with emphasis on the possible relation of vitamin A and estrogen in such changes, and on the origin of replacing epithelium. The Zuckerman hypothesis offering an embryologic explanation for changes observed after estrogen treatment and definitions of metaplasia are briefly considered.

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Aided by research grants from the University of California Board of Research.

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