114 O
. Peulen et al. Livestock Production Science 66 2000 109 –120
alone seems to be responsible for the desquamation 6. Dietary spermine and hormonal secretion
observed. It may also argued that, in mammalian cells,
Modifications of mature intestinal functions and spermine is converted to acetylspermine and that this
enzyme expression during weaning are dependent is rapidly oxidised by polyamine oxidase PAO,
upon genetic, dietary and hormonal factors Lee and yielding spermidine and cytotoxic products. The
Lebenthal, 1983. The question as to whether or not inhibition of PAO by MDL72527, used in order to
dietary polyamines act to evoke these changes should slow down the metabolisation of spermine and thus
be addressed. To answer this question, adrenalec- the synthesis of acetamidopropanal, did not avoid the
tomy was performed Kaouass et al., 1994b. It gut atrophy induced by the ingestion of spermine
reduced the changes in the SAs of disaccharidases Kaouass et al., 1996. Moreover, the intestine of
induced by dietary spermine. Thus, the intestinal rats treated simultaneously with spermine and
postnatal maturation promoted by spermine could be MDL72527 appeared more mature than that of rats
mediated, at least in part, by the adrenal glands. receiving spermine alone.
Nevertheless, adrenalectomy did not completely These findings prove that spermine itself, without
eliminate the spermine-induced appearance of suc- being metabolised to the toxic products mentioned
rase and the increase in the SA of maltase Kaouass above, is responsible for both cell loss observed at 8
et al., 1994b. This may be due to the direct effect of h post-treatment and intestinal maturation observed 3
spermine on the enterocytes see earlier and or to days later. The physiological state of the cell could
factors secreted by tissues other than the adrenal be important in this process since the spermine dose
glands. Furthermore, the spermine-induced decrease used to induce intestinal maturation in suckling rats
in the SA of lactase was not affected by adrenalec- is without effect on the speed of desquamation of the
tomy. Thus, adrenal glands are not involved in the enterocytes in adult animals Peulen et al., unpub-
spermine-induced decrease of lactase SA observed in lished data.
in vivo studies. Thyroxine and bombesin could be implicated in this phenomenon see later.
Since parenteral spermine injection had no effect
5. Direct effect of spermine on the enterocytes on intestinal postnatal maturation Kaouass et al.,
1994a and since the adrenal gland is involved in this Previous results show that dietary spermine acts in
phenomenon, it may be possible that spermine given two phases on intestinal properties in suckling rats.
orally induces intestinal secretion of one or more To know whether these effects are direct i.e.,
substances which, in turn, stimulate the secretion of concern the enterocytes only or indirect i.e., in-
endogenous local factors and or hormones. Results volve hormones, neurotransmitters or local factors,
have confirmed this possibility Kaouass et al., different experiments have been performed. It was
1994b. The ability of spermine to increase corticos- found that: 1 in organ culture, spermine had no
terone output was maximal 5 and 6 h after ingestion, maturational effect on intestinal explants from suckl-
a period during which maximal stimulation of adre- ing rats Kaouass et al., 1994a, 2 spermine
no-corticotropic hormone ACTH output was re- induced maturation in enterocytes isolated from the
corded. This observation suggests that there must be proximal intestine of suckling rats and cultivated in
a link between the digestive tract and the pituitary– ´
synthetic media Wery et al., unpublished results, adrenal axis. This link is not spermine: parenteral
and 3 spermine accelerated the differentiation of spermine administration is ineffective in inducing
CaCo-2 cells Deloyer et al., unpublished results. intestinal maturation and corticosterone secretion
Although inconclusive, these observations indicate Kaouass et al., 1994a. It could be a gastrointestianl
that spermine could have a direct effect on the GI hormone, a cytokine and or the gut nervous
enterocytes but do not exclude an indirect effect see system see earlier.
later. At the present time, we do not know whether The effects of gastrin, cholecystokinin CCK-8,
the polyamine target specific receptor? is intracellu- vasoactive intestinal peptide VIP, neurotensin,
lar or located on the plasma membrane. somatostatin, secretin and glucagon, all intraperitone-
O . Peulen et al. Livestock Production Science 66 2000 109 –120
115
ally injected, were tested Kaouass et al., 1997a. plasma. Nevertheless, a direct action of these cyto-
None of these polypeptides affected brush-border kines on the enterocytes is not excluded: receptors
enzyme SA. Thus, these GI hormones do not seem to for IL-6 are present on the human intestinal epithelial
be involved in spermine-induced intestinal matura- cells Shirota et al., 1990.
tion. From another point of view, there are several
There is increasing evidence for a link between the reports indicating that IL-1b, IL-6 and TNF-a ad-
neuroendocrine and immune systems Rothwell, ministration increases ACTH and corticosterone
1991. Interleukin-1b IL-1b, interleukin-6 IL-6 plasma concentrations in adult animals Rivier et al.,
and tumour necrosis factor alpha TNF-a, poly- 1989; Besedovsky et al., 1991; O’Grady et al.,
peptides predominantly produced by monocytes and 1993. Such observations were also made in suckling
macrophages, have been reported to activate the rats, although IL-1b induced a more marked effect
pituitary–adrenal axis by stimulating the corticot- than did IL-6 and TNF-a. Assuming that this effect
ropin releasing-factor CRF-containing cells in the is mediated in the same way as in adult animals, i.e.,
hypothalamus. In order to assess the possible role of through increasing CRF release, these results show
IL-1b, IL-6 and TNF-a as a link between the that the pituitary–adrenal system is already mature
ingestion of spermine and the activation of the enough in suckling rats to respond to the stimulatory
pituitary–adrenal axis, different experiments were effect of immunological factors.
undertaken. These cytokines also increased the intracellular
The ingestion of spermine produced increases in polyamine concentration Kaouass et al., 1997b. As
plasma concentrations of IL-1b, IL-6 and TNF-a IL-1b activates the ODC contained in intestinal
Kaouass et al., 1997b. The peak responses of IL-1b epithelial cells in vitro, it is possible that the increase
and IL-6, appearing within 6 h after spermine of polyamine content induced by IL-1b and IL-6 is a
administration, corresponded to the peaks in plasma consequence of a direct action of these cytokines on
corticosterone and
ACTH concentrations.
This the intestinal ODC activity. Nevertheless, it cannot
ACTH peak could be a result of IL-1b action be excluded that an indirect action of IL-1b and IL-6
Uehara et al., 1987. The increases in plasma on the intestinal polyamine concentration occurs
concentrations of IL-1b, IL-6 and TNF-a were all through an increase in plasma concentration of
observed at the same time; as it has been shown that corticosterone. The latter is known to be an activator
IL-1b and IL-6 can induce TNF-a release Wong of ODC.
and Clark, 1988, it cannot be excluded that the The indirect action of spermine, via factors other
action of spermine on TNF-a release was mediated than corticosterone, on the enterocytes is not ex-
by IL-1b and or IL-6. cluded: the administration of IL-1b to the rats
Thus, it may be suggested that spermine ingestion induced release of insulin and prostaglandins Ue-
by unweaned rats stimulates the secretion of IL-1b, hara et al., 1987, both of which are involved in
IL-6 and or
TNF-a, from
the gut-associated-
postnatal intestinal maturation. Cytokines other than lymphoid-tissue GALT system. These substances
IL-1b and IL-6 could also play a role in this effect. then appear in the general blood circulation and
could increase corticosterone secretion, thus trig- gering the intestinal maturation process. This possi-
7. Effect of dietary spermine on the nervous
