title: Ghrelin and GHS-R in the rat gastric mucosa: Are they involved in regulation of growth during early weaning?
abstract: OBJECTIVE
  Based on previous evidence showing that early weaning disturbs the ontogenesis of rat gastric glands, which are the major site of ghrelin synthesis, we investigated the distribution of ghrelin and its receptor (GHS-R) in the rat gastric epithelium during postnatal development and evaluated the effects of early weaning on their levels. Additionally, we studied the contribution of ghrelin to gastric growth during the abrupt nutrient transition.
  
  
  METHODS
  Wistar rats were submitted to early weaning at 15 d and suckling counterparts were taken as controls.
  
  
  RESULTS
  By running quantitative reverse transcription polymerase chain reaction, immunoblots, and immunohistochemistry, we detected a variation of ghrelin levels and an increase of expression and number of immunolabeled cells, 3 d after treatment (P < 0.05). Through confocal microscopy, we identified GHS-R in the neck region of the gland and did not observe changes in protein levels. Growth was evaluated after ghrelin antagonist ([D-Lys-3]-GHRP-6) administration, which reduced DNA synthesis index in early-weaned rats (P < 0.05) as determined by bromodeoxyuridine incorporation.
  
  
  CONCLUSIONS
  The present study demonstrated that ghrelin and GHS-R are distributed in gastric mucosa during the postnatal development, indicating that they can signal and function in epithelial cells. We concluded that early weaning increased ghrelin levels in the stomach, and it takes part of cell proliferation control that is essential for stomach growth. Therefore, among the many effects previously described for early weaning, this abrupt nutrient transition also changed ghrelin levels, which might represent an additional element in the complex mechanism that coordinates stomach development.
authors.affiliation: Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Natália Martins Valente Ramos
authors.initials: NM
authors.lastname: Bittar
authors.affiliation: Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Juliana Guimarães
authors.initials: JG
authors.lastname: Zulian
authors.affiliation: Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Daniela
authors.initials: D
authors.lastname: Ogias
authors.affiliation: Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil. Electronic address: Patgama@usp.br.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Gama
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism; D005753:Gastric Mucosa / Q000254:growth & development / Q000378:metabolism*; D054439:Ghrelin / Q000378:metabolism*; D017208:Rats, Wistar; D054440:Receptors, Ghrelin / Q000378:metabolism*; D015398:Signal Transduction; D013270:Stomach / Q000254:growth & development; D014886:Weaning
chemical_list: D054439:Ghrelin; D054440:Receptors, Ghrelin
keywords: Cell proliferation; Ghrelin; Stomach; Suckling; Weaning; [d-Lys-3]-GHRP-6