Postnatal changes in ghrelin mRNA expression and in ghrelin-producing cells in the rat stomach

Abstract

Ghrelin was recently isolated from the rat stomach as an endogenous ligand for the GH secretagogue receptor. Although it is well known that a large amount of ghrelin is produced in the gastrointestinal tract, developmental changes in ghrelin mRNA expression and differentiation of ghrelin-immunopositive (ghrelin-ip) and mRNAexpressing (ghrelin-ex) cells in the stomach have not been elucidated.In this study, we therefore investigated the changes in ghrelin mRNA expression levels and in the numbers of ghrelin-ip and -ex cells in the stomachs of 1-to 8-week-old male and female rats by Northern blot analysis, immunohistochemistry and in situ hybridization. Northern blot analysis showed that the level of weak ghrelin mRNA expression was low in the postnatal period but then increased in a dimorphic pattern, i.e. transient stagnation at 4 weeks in the male rats and at 5 weeks in the female rats. The number of ghrelin-ip and ghrelin-ex cells also increased after birth, and more numerous ghrelin cells were found in female rats than in male rats, and this finding was confirmed by Northern blot analysis. Ghrelin-ip and -ex cells first appeared in the glandular base of the fundic gland and then they were found in the glandular base and the glandular neck at 3 weeks of age, suggesting that the distribution of ghrelin cells is extended from the glandular base to the glandular neck during the postneonatal development period. This is the first report on detailed changes in postneonatal ghrelin expression level and in the number of ghrelin cells in the rat stomach. The sexual dimorphism of ghrelin expression and ghrelin cell differentiation suggest that ghrelin plays an important physiological role in the stomach.

Ghrelin in the gastrointestinal tract and blood circulation of perinatal low and normal weight piglets

“…These results contrast with a study on rodents, in which the GCs spread from the base to the neck of the gastric glands with increasing age (Sakata et al, 2002b). Nonetheless, a recent study did observe this spreading in the oxyntic mucosa in older pigs (from 28 days to 7 months of age) (Vitari et al, 2012).…”

“…Ghrelin immunoreactive (IR) epithelial cells have been observed from the stomach to the colon in perinatal rodents (Sakata et al, 2002a), humans (Rindi et al, 2002) and postnatal cattle, such as sheep, pigs and horses (Hayashida et al, 2001;Vitari et al, 2012). In the gastric mucosa of rodents, the ghrelin cells (GCs) get distributed from the glandular base to the glandular neck when rat pups grow older (Sakata et al, 2002b). Its perinatal presence and important physiological and endocrine functions indicate that ghrelin might play a role in the gastrointestinal development and possibly also in its IUGR-associated adaptations (Wang et al, 2005).…”

Characteristic features of ghrelin cells in the gastrointestinal tract and the regulation of stomach ghrelin expression and production

“…Accordingly, ghrelin-ip and ghrelin mRNAexpressing cells were also observed just after birth [20] . At 1 wk of age, these ghrelin cells were mainly localized in the glandular base of the fundic gland, and then the distribution of ghrelin cells gradually extended from the glandular base to the glandular neck with increasing age in both sexes [20] .…”

“…Given that a significant increase in estrogen concentration in the portal vein compared with that in the artery was observed in intact rats, but not in gastrectomized rats [22] , the concentration of gastric estrogen must be higher than that of plasma estrogen. Moreover, neither the gastric ghrelin expression nor the plasma [20] . The data in (A) and (B) are shown as the % of 1-wk-old (1 wk) rats (100%) and each bar represents the mean ± SE (n = 3).…”

“…At 1 wk of age, these ghrelin cells were mainly localized in the glandular base of the fundic gland, and then the distribution of ghrelin cells gradually extended from the glandular base to the glandular neck with increasing age in both sexes [20] . An interesting finding in that study was that two kinds of stained ghrelin cells, weakly stained and strongly stained cells, were found in female rats at the early stage of development (1 and 3 wk of age), whereas staining in most of the ghrelin cells was strong in male rats and 7-wk-old female rats [20] . With increasing age, weakly stained cells were replaced by [16] .…”