ONE FlGUREAt the beginning of the third week of postnatal life in the mouse, the alkaline phosphatase of the duodenal epithelium undergoes a sudden upsurge that carries it to the maximal level of the entire life history. The finding that this upsurge can be brought about earlier than usual by experimental treatments that apparently cause emotional stress led to the hypothesis, stated at the close of the second paper of this series (Moog, '51), that the increase of phosphatase in the duodenum is directly controlled by steroids from the adrenal cortex and thus indirectly by the pituitary through its adrenocorticotrophic hormone (ACTH) . The present paper comprises a series of tests by which that hypothesis has been substantiated.Three ways of determining whether the pituitary and adrenal glands intervene in the functional differentiation of the duodenum immediately suggest themselves. The first is to administer cortisone to nursling mice to see if, and when, the phosphatase content of the intestine is affected. The second is to remove the adrenals during the nursling period t o see whether the rise of phosphatase is interfered with. The third is to administer ACTH to determine whether this Aided by a grant from the Rockefeller Foundation. 329 FLORENCE MOOGfactor, which presumably acts by way of the adrenals, also affects the duodenal phosphatase. All three of these tests have been applied in the studies reported in this paper. METHODS 1.Aminznls. The mice used were of a white Swiss strain that has been maintained in this laboratory by close inbreeding for about 15 generations. The colony is kept on Purina Laboratory Chow, supplemented by leafy green vegetables. Phosphutuse uitd mitrogen ~l e t e r~i~a u~~o m s .Methods of killing and of determining phosphatase activity and nitrogen concentration were as reported previously (Moog, '50, '51). At sacrifice each animal was weighed and its sex recorded; but no sex difference was indicated in the results of any experiment in this series.3. Hormone admisistrution. Cortisone was given as a single intraperitoneal injection a t the rate of 0.15mg (0.03 ml of a 5 mg/ml suspension) per 5 gm of body weight. Controls either were untreated or received injections of saline with 1.5% benzyl alcohol, the preservative contained in the cortisone suspensions. ACTH was given intraperitoneally * I am indebted t o Dr. Elmer Alpert and Mr. J. P. Badgett of Merck and Co. f o r a generous supply of cortisone acetate, and to Dr. Edvtin E. Hays of The Armour Laboratories for a gift of ACTH.The adrenalectomies nere skillf uily pcrf ormed by C . Jackson Bennett.

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Previous investigations have shown that cortisone or thyroxine can promote maturation of the intestinal epithelium in rats hypophysectomized a t six days of age. This indication that either the thyroid or the adrenocortical hormone can act in the absence of the other has been pursued by study of intestinal maturation in rats deprived of the thyroid or adrenal glands during the suckling period. At 24 days of age, rats that have been thyroidectomized at six days retain the short villi and low mitotic index characteristic of neonatal life. Thyroxine elevates the mitotic index; neither thyroxine nor cortisone promote lengthening of the villi, but both cause some deepening of the crypts. Duodenal alkaline phosphatase and jejunal maltase remain a t very low levels, but sucrase, which is absent at six days, does appear in the thyroidectomized pups at 24 days. Thyroxine raises phosphatase and maltase activity to the normal 24-day level, but cortisone is only partly effective. Sucrase is raised above the normal maximum by cortisone but not by thyroxine. After adrenalectomy a t 14 days, cortisone corrects deficiencies in villus height, crypt depth, and mitotic index, but thyroxine is without effect. Phosphatase, maltase, and sucrase activities rise only to subnormal levels in adrenalectomized pups. Thyroxine restores phosphatase activity to the control level, but is only partly successful in normalizing disaccharidase activities. Periodic acid-Schiff stainability of the brush border is weak in specimens deprived of either thyroid or adrenals. Both thyroxine and cortisone restore normal intensity after thyroidectomy; after adrenalectomy only cortisone was able to restore normal stainability. Plasma corticosteroid concentration is elevated by thyroxine only if the hypophysis is present. These results demonstrate that the intestinal epithelium is able to respond to each hormone in the absence of the other.

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