Influence of Secretin and Pentagastrin on the Circadian Rhythm of Cell Proliferation in the Intestinal Mucosa in Rats

Abstract

The effects of Secretin (3.5 U/100 g) and Pentagastrin (25 μg/l00 g) on cell renewal in jejunal mucosa was studied in male Wistar rats. The labeling index (LI), mitotic index (MI), and histogram of the distribution of labeled cells were measured at 4-hour intervals during 24 h after intraperitoneal injection of hormones and compared with results obtained in control animals. DNA label was obtained by injection of tritiated thymidine (70 μCi/100 g) 30 min before sacrificing the animals. The proliferation of intestinal cells in rats was marked by a circadian rhythm with a nocturnal peak of DNA synthesis. After Pentagastrin, the LI remained high for 16,20, and 24 h after injection, during the time the control levels diminished in the circadian rhythm. The normal MI and the enlargement of the zone of proliferation support the hypothesis of a stimulating effect of gastrin on intestinal cell renewal. After Secretin, the LI peak of the cycle was suppressed and the MI decreased, indicating an inhibiting effect of Secretin on intestinal cell renewal. Secretin and gastrin act as trophic factors on intestinal mucosa and produce opposite effects on cell proliferation.

Effect of Somatostatin on Normal and Gastric-Stimulated Cell Proliferation in the Gastric and Intestinal Mucosae of the Rat

“…mucosae. It was noted that all LI for duodenal and jejunal mucosae were lower at 1 a.m. than at 5 a.m. Tills was probably related to a nyc théméral variation in this proliferative param eter, already described (4,22).…”

“…Infusion was done during the night to emphasize the possible inhibitory effect of somatostatin since the maximal activity of DNA synthesis was registered at about 0 2 a.m. in the gastrointestinal tract of the rat (22); the period of 8 h was chosen to be approxi mately equal to the duration of the DNA synthesis phase.…”

“…29. 31); some actions of other gut hormones, like secretin and glucagon, on gastrointestinal cell proliferation have also been reported (12,13,22). With the finding that a neural polypeptide such as somatostatin, a growth-hormone-release-inhibiting factor (3), was also present in the stomach, intestine and pancreas (11,16,21,23,26), the multiplicity of its possible target organs and its eventual role in the gastrointestinal cellular balance has be come an interesting question.…”

Effect of Fasting and Somatostatin Administration on Circadian Rhythms of Jejunal Cell Renewal and Plasma Gastrin Level in Rats

“…Labeling index and mitotic index, i.e. the percentage of labeled cells and mitotic figures in the proliferative compartment were easily estimated as the prolifera tive zone and predetermined as the first 30 cells of the crypt [16].…”

“…18]. both trophic hormones of the intestine [3,10,12,16]. In gastric [17,20] while ultradian variations with two major peaks each day characterized the growth hormone release [22].…”