SUMMARY1. Positional and temporal correlates for the development ofmicrovillus membranes and for two of the hydrolytic enzymes they contain have been determined and compared with the ability of enterocytes to transport valine during migration from crypt base to villus tip in jejunal tissue taken from rats maintained on diets containing different amounts of protein.2. Microvillus elongation and the appearance of both aminopeptidase N (APN) and isomaltase (IM) activities reached maximal rates of expression in enterocytes located 16 + 5,m from the crypt-villus junction. This close positional correlation was not found for the later development of the valine transport function.3. Feeding rats isoenergetic diets containing 20 % instead of 5 % protein caused significant increases in both villus height and crypt depth without changing the positional correlations described above.4. The maximal rates for microvillus elongation and APN and IM appearance were greater and occurred earlier in enterocytes taken from rats fed a high-protein diet. The time of onset and capacity to transport valine were found to be closely correlated for rats maintained on high-and low-protein diets.5. The ratio of APN to IM activity in fully differentiated enterocytes was either 0 7 or 1-2 depending on whether rats had been fed a low-or high-protein diet. The maximal length of microvillus membranes in fully differentiated enterocytes from rats on a low-protein diet was 1-4 times that found in rats maintained on a high-protein diet.6. Possible ways in which the microvillus membrane structure of enterocytes, enzyme activity and the ability to transport amino acids might be controlled are discussed. Relative estimates are also made of the probable effects that changes in diet will have on the capacity of the intestine to digest and absorb nutrients.

SUMMARY1. The influx of serine, alanine and methionine across the brush border membrane of the rabbit ileal mucosa has been measured during short periods of incubation.2. A kinetic analysis of the uptake data, assuming one mediated entry mechanism or one mediated entry mechanism plus a diffusion component to be present, does not provide an adequate explanation for the results obtained. Methionine inhibition of serine uptake provided direct evidence that the diffusive entry of serine into the rabbit ileum was small or non-existent.3. Data taken from amino acid inhibition and substrate-uptake experiments, fitted simultaneously to a double hyperbolic model of amino acid uptake, give good agreement between predicted and experimental results. There is also good quantitative agreement between computer-derived kinetic constants in the present work and similar constants obtained previously using a different method of analysis.4. Present work supports the general hypothesis that neutral amino acids use two mediated pathways to enter the rabbit ileal mucosa. The possible physiological significance of these results and their probable effect on currently held concepts of how amino acids cross the brush border membrane of the rabbit intestinal mucosa is discussed.

SUMMARY The uptake of cortisol by the gastro-intestinal tract and by the liver was estimated in sheep by measurement of [3H]cortisol concentrations in portal and hepatic venous plasma during constant infusion of tritium-labelled cortisol, with simultaneous measurement of plasma flows. The total splanchnic uptake of cortisol was 57 ± 4 (s.e.m.)% of the measured rate of cortisol secretion, 45% by the liver and the remainder by the gastro-intestinal tract. The splanchnic extraction of cortisol could be related to plasma flow, and was less efficient at higher flows. It could also be related to plasma cortisol concentration, and was more efficient at higher concentrations. The splanchnic uptake of cortisol was closely correlated with the flow of unbound cortisol into the region, and was 1·61 times that influx. There is therefore partial dissociation of plasma protein-bound cortisol during the splanchnic uptake. About 25% of secreted cortisol is converted to cortisone at extrahepatic sites, and is removed from plasma by the liver.

Albumin was isolated from ovine plasma and its affinity for cortisol was determined by equilibrium dialysis at 37\ s=deg\ . The value of Ka[\g=s\pa] for a 1 % (w/v) albumin solution was 0\m=.\275which is similar to the value for human plasma albumin.The affinity constant of transcortin in ovine plasma was determined by equilibrium dialysis of diluted plasma at several concentrations of cortisol. The value found, Kt (37\s=deg\) = 0\m=.\87x 108 l./mole, is close to that found for human plasma transcortin by Mills (1962).The concentration of transcortin in ovine plasma, expressed as cortisolbinding capacity, was 6\p=n-\49 \g=m\g.(mean 24 \g=m\g.)cortisol/l. These concentrations are much lower than those found in human plasma. The observation of Lindner (1964) that cortisol binding capacity did not increase during pregnancy in sheep has been confirmed.In sheep which were accustomed to handling, the mean concentration of cortisol in plasma was 17\m=.\8 \g=m\g./l. and of this amount 59% was bound to transcortin, 19 % to albumin and 22 % was not bound to protein.

SUMMARY Tritium-labelled cortisol was infused intravenously for about 4 hr. into sheep with autotransplanted left adrenal glands. The specific activity of plasma cortisol became constant about 2 hr. after beginning the infusion, and in almost all experiments, the rate of cortisol secretion and the concentration of cortisol in plasma were constant during the remainder of the period of infusion. The rate of cortisol turnover was calculated as the ratio of the rate of infusion of labelled cortisol and the constant specific activity which was attained during infusion. Within the limits of experimental error, the calculated rate of cortisol turnover in 55 experiments was equal to the simultaneously measured rate of cortisol secretion. In sheep which were accustomed to handling, the rate of cortisol secretion was about 12 μg./min. and the concentration of cortisol in plasma was about 18 μg./l. The rate of cortisol secretion did not change during pregnancy in ewes, but there was a decrease in the concentration of cortisol in plasma in the last 2 weeks before lambing.