The functional differentiation of the small intestine. III. The influence of the pituitary‐adrenal system on the differentiation of phosphatase in the duodenum of the suckling mouse

Abstract

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.

Biochemistry of Intestinal Development

“…Figure 4 shows that this adult characteristic of glucocorticoid-independence appears on day 17-18, i.e., very soon after the sucrase rise begins. Similar results have been reported for alkaline phosphatase in mouse duodenum (42 sitivity to certain toxic substances at this time is equally intriguing.…”

“…Administration of glucocorticoids to suckling rats or mice causes precocious increases in the activities of sucrase (40, 56,57), maltase (56,58), trehalase (56), amino peptidase (43,56), and alkaline phosphatase (42), as well as precocious disappearance of various lysosomal hydrolases (59), and the capacities for pinocytosis (15,19,60) and for the absorption of intact immunoglobulins (19,61). Conversely, it has been shown that if animals are adrenalectomized during the second postnatal week, the usual decrease of pinocytosis (62) and increase ofalkaline phosphatase (42) and sucrase (63) activities are largely prevented.…”

Intestinal Lactase Synthesis during Postnatal Development in the Rat

“…however, led to significant insight into a completely different control mechanism regulating intestinal maturation. In a series of experiments involving the enforcement of premature weaning (33), adrenalectomy (34), and pituitary ablation with exogenous hormone replacement (35), a combined or interdependent effect of glucocorticoids and thyroxine on the maturational patterns of intestinal enzymes, such as alkaline phosphatase and lactase, was demonstrated. The mechanism by which these hormones have their effects remains elusive (36), but may involve changes in lactase synthesis rate.…”

Developmental Changes in Murine Brain Antioxidant Enzymes

“…The lower activities and higher protein levels at earlier developmental ages may be related to the fact that catalase may be dependent on a cofactor for activation, which may itself be developmentally regulated with low levels at earlier ages. As aging progresses beyond young adulthood, studies have shown a reduction in total antioxidant reserve and efficiency of the normally protective endogenous defense system throughout later life (22,24,25). Neuronal cells therefore become more vulnerable to acute oxidative injury, and this contributes to the deleterious effect seen in older, more mature brains exposed to traumatic or ischemic brain injury.…”