Distribution of ghrelin and GHS‐R in the rat gastric mucosa: effects of early weaning and consequences to growth control

Abstract

During postnatal development, maternal milk is the main source of nutrients, hormones and factors that promote growth and the functional maturation of the gastrointestinal tract. Early weaning is the abrupt interruption of suckling and it changes the development of the stomach, which represents the major site of ghrelin synthesis. In the present study, we evaluated the short‐term effects of early weaning on gastric ghrelin concentration and conducted a detailed investigation on the distribution of growth hormone secretagogue receptor (GHS‐R) in the rat gastric mucosa during the third postnatal week. In addition, we studied whether ghrelin is part of cell proliferation and differentiation control in gastric epithelium, and to that we used a receptor antagonist. We observed an increase of ghrelin immunostained cells in pups submitted to early weaning. After RT‐PCR, we observed that GHS‐R expression was not altered by dietary change and this result was confirmed through Western blot. We also identified GHS‐R immunolabeled cells along the gastric gland. The antagonist [D‐Lys‐3]‐GHRP‐6 reduced DNA synthesis index, as determined by BrdU incorporation followed by immunohistochemistry, but it did not alter mucous neck cell differentiation. Therefore, we found that ghrelin and GHS‐R are distributed in the gastric mucosa during the third postnatal week and that early weaning increased hormone levels in the gastric epithelium, without changing its receptor. We suggest that ghrelin modulation might be involved in the control of cell proliferation, which is essential for stomach growth. Supported by CNPq and FAPESP (2011/17415–3; 2011/07089–1).