Induction of Gastric Ornithine Decarboxylase in Early Weaning Rats

Abstract

Background/Aims: Early weaning has been shown to induce intestinal ornithine decarboxylase (ODC) activities and cell proliferation in rats. No information is available about the effect of early weaning on ODC activity in the stomach. Methods: Suckling rats were prematurely weaned on postnatal day 15 and followed through day 21. Oxyntic gland mucosa of stomach was obtained on postnatal days 15, 16, 18 and 21 (days 0, 1, 3 and 6 after early weaning) and assayed for ODC activity, DNA, protein and pepsinogen activity. α-Difluoromethyl ornithine (DFMO), a specific ODC inhibitor, was given orally to early-weaned pups and its resultant effects were assessed on days 1 and 6 after early weaning. Results: Stomach mucosal wet weight, DNA, protein and pepsinogen activities significantly increased on day 6 after early weaning. ODC activity increased on days 1, 3, and 6 after early weaning, with the highest increase (3-fold) on day 1 when compared to controls. The increases of ODC activity, DNA and protein contents as induced by early weaning were significantly suppressed when pups were exposed to DFMO. However, no suppression of pepsinogen activity was observed. Conclusions: Our study shows that early weaning induces ODC activity and functional growth in the stomach. Gastric ODC activity is essential in gastric mucosal growth processes but not in differentiation. The induction of stomach ODC may act as an early marker in the growth of stomach mucosa induced by early weaning in rats.

MAPKs and Signal Transduction in the Control of Gastrointestinal Epithelial Cell Proliferation and Differentiation

“…Although their physiological relevance in milk has been debated, both EGF and TGFβ are able to activate the respective signaling cascades through MAPKs and Smads in different organs [71,72,129,130,133]. In addition, disturbances of suckling change the stimuli and modify the output of MAPKs pathway, in a way that during early weaning, ERK1/2 and Src phosphorylation are amplified in gastric cells, and such condition results in increased cell proliferation and differentiation [71,72], and may contribute to the functional induction of ornithine decarboxylase in the gastric epithelium [135]. …”

MAPK Signaling Pathway Regulates p27 Phosphorylation at Threonin 187 as Part of the Mechanism Triggered by Early-Weaning to Induce Cell Proliferation in Rat Gastric Mucosa

“…Milk-borne molecules and feeding pattern have emerged as important keys in the regulation of different cellular processes in the gastric epithelium during postnatal development [15]–[19]. Interestingly, when suckling is interrupted by early weaning, several effects are observed in the rat gastric mucosa, such as the rapid differentiation of mucous neck cells [15], the augment of pepsinogen and ornithine-decarboxylase activities [16], and increased cell proliferation [17]. Moreover, we have previously shown that early weaning also influences the expression of growth factors and activation of signaling pathways.…”

O papel do alimento, do fator de crescimento transformante alfa e do receptor do fator de crescimento epidermal na proliferação e diferenciação celular durante o desenvolvimento pós-natal do epitélio gástrico de ratos.

“…No mesmo estudo, verificou-se que quando os animais desmamados precocemente são submetidos ao jejum, ocorre inibição da proliferação celular, resposta inversa à observada em animais amamentados normalmente e semelhante à encontrada no rato adulto (Gama e Alvares, 2000). Lin et al (2001) observaram o aumento de atividade da enzima ornitina descarboxilase (ODC) no estômago após o desmame precoce e sugeriram que esse efeito pode ser um importante indicador das modificações gástricas que ocorrem com a mudança da dieta. Em conjunto, esses resultados mostram que o desmame precoce pode acelerar o aparecimento de respostas celulares típicas de um animal adulto, e ainda que o leite pode agir como um modulador do crescimento e da renovação da mucosa gastrintestinal (Lin et al, 1998;Gama e Alvares, 2000).…”

“…Yeh et al (1986) e Lin et al (1998 observaram altos níveis de corticosterona logo após o início do desmame precoce seguido de um aumento na atividade de sacarase, enzima intestinal utilizada como marcadora de diferenciação na transição amamentação-desmame. No estômago, a atividade do pepsinogênio é maior nos filhotes desmamados precocemente (Lin et al, 2001) e esse aumento também ocorre após a elevação do corticóide. Takeuchi et al (1981) e Peitsch et al (1981) mostraram que a alteração da dieta aos 13 dias de vida não modifica os níveis de gastrina, porém aumenta a quantidade de receptores para esse hormônio na mucosa gástrica.…”

“…O desmame precoce induz outras modificações no epitélio gastrintestinal, destacando-se o aumento na atividade de enzimas intestinais e gástricas (Lee e Lebenthal, 1983;Lin et al, 1998Lin et al, , 2001, o que sugere maturação acelerada da mucosa. Como os níveis de corticosterona aumentam logo após o desmame precoce, é possível que esse hormônio esteja envolvido no amadurecimento acelerado, uma vez que as alterações enzimáticas no estômago e no intestino ocorrem somente após a elevação da corticosterona (Yeh et al, 1986;Lin et al, 1998).…”