116 O
. Peulen et al. Livestock Production Science 66 2000 109 –120
stimulated growth of the small intestine i.e., in- Indeed, injection of hormones as corticosterone
creased intestinal weight and length, and intestinal Martin and Henning, 1982, insulin Buts et al.,
protein and DNA contents. It also induced appear- 1988, prostaglandins Neu et al., 1983 or insulin-
ance of sucrase, an increase in maltase SA and a like growth factor-I IGF-I Young et al., 1990,
decrease in lactase SA. usually enhances the SA of intestinal lactase in
The mechanism by which bombesin affects intesti- suckling animals. These findings suggest that, like
nal development is unknown. Specific receptors to thyroxine, bombesin can be involved in the decline
this neuropeptide are present on intestinal en- of lactase SA during the period of weaning.
terocytes Moran et al., 1988. Thus, a direct action Other arguments confirm that that dietary sper-
of bombesin on enterocyte metabolism cannot be mine could affect the nervous system of the gut.
excluded. Bombesin could also modify intestinal Putrescine can be metabolised to g-aminobutyric
functions via endogenous growth factors or hor- acid GABA and the endogenous phosphorylation of
mones, such as polyamines Grillo, 1985 and cor- the GABA type A receptor is modulated by spermine
ticosterone Henning, 1981. Indeed, plasma con- Bureau and Laschet, 1995. In preliminary experi-
centrations of corticosterone and intestinal levels of ments El Khefif et al., unpublished results, we
intracellular polyamines were enhanced when bom- showed that spermine modified intestinal motility in
besin was administered to the animals Kaouass et suckling and adult rats, and that muscimol, a GABA
al., 1997a. Adrenalectomy in bombesin-treated rats agonist, produced an intestinal desquamation similar
generally decreased the disaccharidase SA. to the type caused by spermine but followed by
As the effect of bombesin on corticosterone regeneration without the appearance of adult forms
secretion could be mediated in the same way in adult of enterocytes.
animals, i.e., through an increase in ACTH release Consequently, dietary spermine could act indirect-
see earlier, it was questioned whether or not blood ly on the enterocytes, by way of the nervous system,
and intestinal bombesin concentrations are modified at the first stage of its action in the small intestine.
by spermine treatment. It was shown that this polyamine had no apparent action on the concen-
tration of bombesin in plasma Kaouass et al.,
8. Effect of dietary spermine on the immune
1997a. However, the intestinal content of bombesin system
was significantly decreased. Since this change in intestinal bombesin coincides with the increase in
The immune system could be influenced by sper- plasma corticosterone concentration, produced by
mine ingestion as suggested by Kaouass et al. spermine ingestion, the existence of a relationship
1997b and by Peulen and Dandrifosse 2000 in between the two phenomena, by the way of the
rats see earlier: the effects of interleukins on post- nervous system, was suggested. The more plausible
natal intestinal maturation. This was confirmed by hypothesis is that spermine stimulates the secretion
studies performed in suckling mice. Indeed, Ter of bombesin from enteric nerves in the synaptic cleft
Steege et al. 1997 have proven that the percentage where bombesin could act directly on the enterocytes
of intra-epithelial lymphocytes expressing the T-cell and or on a postsynaptic nervous receptor with, at
receptor ab TCRab, clusters of differentiation the end, activation of the pituitary–adrenal axis.
CDs-4, -5 and -54, as well as the levels of Afterwards, this neuropeptide would be rapidly
expression of these antigens, increased similarly after catabolised ‘‘inactivated’’.
spermine ingestion to that seen with normal matura- Based on these findings, the effect of spermine on
tion. corticosterone secretion could partly be mediated
The effect of spermine and or spermidine on through an enteric-nerve neurotransmitter-dependent
human lymphocyte differentiation and proliferation mechanism in which bombesin would be implicated.
has also been studied. Spermine inhibited DNA The fact that bombesin decreases lactase SA is
synthesis by lymphocytes isolated from the tonsils of important since that is the first time that it has been
children and
then stimulated
by a
mitogen demonstrated that an endogenous factor, other than
phytohaemagglutinin L, but only in the presence of thyroxine, can affect this parameter in that way.
bovine serum El Khefif et al., 1995. In serum-free
O . Peulen et al. Livestock Production Science 66 2000 109 –120
117
medium which supports in vitro proliferation of all the modifications observed in the pancreas after
human T cells stimulated by the same mitogen, feeding spermine to suckling rats are similar to those
spermine induced proliferation of these cells. It also observed in normal pancreatic maturation. Thus, it
acted on the differentiation of the latter. Indeed, may be proposed that spermine treatment induces
when spermine was added to culture media, a maturation of the pancreas in suckling rats as it does
decrease in the expression of the IL-2 receptor for the intestine.
CD25 marker and of the transferrin receptor CD71 The effect of spermine on intestinal maturation
marker was observed, whereas the CD4 CD8 ratio could involve at least the activation of ACTH and
was not modified. Under the same experimental corticosterone secretion. As the latter could have an
conditions, the expression of the CD23 marker of B effect on pancreas or liver maturation, in the experi-
lymphocytes was not affected. ments described below, hepatic properties were
analysed after feeding spermine to suckling rats. Putrescine and spermidine contents were higher in
9. Effect of dietary spermine on postnatal the livers of pups than of adults, while liver spermine
