No abstract

SummaryThe use of prostaglandins in pharmacolo~ic doses to maintain Several markers of growth and biochemical development in the rat were studied after administration of prostacyclin (PG12) and 16, 16-dimethyl prostaglandin Ez (16, 16DM PGE2). Intermittent administration of PGIz for 3 days to 10-and 19-day-old animals, with subsequent sacrifice at 14 and 23 days, resulted in significant dose related decreases in growth at 23 days. Total sucrase and maltase (glucoamylase) activities were elevated compared to controls at 14 days. Total activities of these enzymes were decreased in postweaned 23-day-old animals, but specific activities per mg intestinal protein were not significantly different. 16, 16DM PGEz administered continuously between day 10-16 of life caused alterations in growth as well as increases in sucrase and maltase (glucoamvlase) activities. Exoeenouslv administered prostaglan- A paucity of data exists concerning the physiologic role of prostaglandins in the gastrointestinal tract of the developing fetus and neonate. Although these compounds elicit potent pharmacologic responses and are ubiquitous in the body, their therapeutic use causes some concern.In adult animals prostaglandins may influence many aspects of gastrointestinal function including motility, secretion, mucosal blood flow, mucous production, and ulcer formation (1). Both PGE and lesser amounts of PGF are present in the organs of the G I tract (2, 13). PGIz is also found in the rat stomach (12). It has gastric antisecretory and cytoprotective properties similar to those of PGEz (14).There is speculation that prostaglandins may protect the small intestinal mucosa from luminal insults by regulating mucous secretion. Robert (15) has shown that prostaglandins may have a "cvtoprotective" effect on the G I tract. Gastric and small intestinal ulcers' can be prevented, in a dose-dependent fashion, by oral and subcutaneous ~rostaalandin administration.If the prostaglandFns play an important role in vascular homeostasis, then alterations in their synthesis or pool sizes might produce aberrations in blood flow and pathologic consequences. Indomethacin decreases the rate of formation and changes the composition of gastric mucus in the dog, making it more susceptible to damage by acid and peptic digestion (10). It is known that synthesis of the mesenteric vasodilators PGE, and PGIz are blocked by indomethacin (3). It is, therefore, of concern that the use of prostaglandin inhibitors such as indomethacin might lead to an increase in the incidence of NEC by compromising mesenteric blood flow. ductal patency in neonates withAcyanotic congenital heart disease has been associated with side effects. Among these side effects are pyrexia, apnea, cutaneous flushing, hypotension, and long bone periosteal proliferation. The long term effects of exogenous administration of the prostaglandins on the development of the rapidly growing mammal is poorly understood.The purpose of this investigation was to: ( 1 ) use an animal model to study the effects of certain p...

ABSTRACT. Previous studies have suggested similarities between the effects of exogenously administered glucocorticoids and prostaglandins in the developing rat small intestine. In this study the effects of exogenously administered glucocorticoids and prostaglandins were compared. In addition, the effects of prostaglandins in adrenalectomized rats were evaluated. Members of both classes of compounds stimulate small intestinal disaccharidase activities, and increase RNA to DNA ratio and brush border membrane protein synthesis. Hydrocortisone accelerates enterocyte turnover, whereas prostacyclin does not. Enteral administration of 16,16-dimethyl prostaglandinEz stimulates disaccharidase activities in intact as well as shamoperated and adrenalectomized animals. The data suggest that certain prostaglandins may play a role in small intestinal metabolism which is similar to that of the glucocorticoids but is independent of the adrenal-intestinal axis. Glucocorticoids are known to play a significant role in the development of small intestinal biochemical function. These hormones appear to mediate a series of enzymatic changes in the small intestine of rats during the 3rd wk of postnatal life (I-3). Administration of hydrocortisone or ACTH during the 2nd postnatal wk causes precocious appearance of sucrase activity (4), whereas adrenalectomy at this time markedly slows the usual increase of sucrase activity (5). In adult rats, sucrase activity is independent of glucocorticoids (6).In a previous study by our group (7), prostaglandins were administered to suckling rats to determine their effects on growth and development. Analysis of small intestinal hydrolase activities demonstrated effects similar to those of the glucocorticoids. Other than this, little information is available regarding the physiological role of prostaglandins in the gastrointestinal tract of the developing fetus and neonate. More recent studies by Koelz (q a/. (8) have demonstrated that an enterally administered prostaglandin analog, 16,l 6-DMPGE2, will stimulate disaccharidase activity in the small intestine of suckling but not adult rats.Since the stimulation of the enzyme activities by the glucocorticoids and prostaglandins are similar in many respects, we decided to investigate further the comparative effects of these two classes of compounds. The purpose of these studies was