Endotoxin (LPS), a membrane component of gram-negative bacteria produces mu
ltiple endocrine and metabolic effects that mimic those seen in acute sepsi
s. It induces species-dependent alterations of the growth hormone (GH) axis
that may participate in the shift of the metabolism towards catabolic even
ts. Humans and sheep show increased GH secretion in response to LPS, as opp
osed to rats, which have been the most studied. The purpose of our work was
to evaluate the effects in intact rams of an acute intravenous administrat
ion of a high dose of LPS on the insulin-like growth factor (IGF)-I/IGF-bin
ding proteins (IGFBPs) system and to analyse the temporal relationship of G
H axis changes with those of several hormonal and metabolic parameters such
as somatostatin, cortisol, insulin, and glucose.
LPS induced a late moderate decrease of total IGF-I plasma levels following
a 5-h steady-state period (-26.6 +/- 4.2%, P<0.05, 9 h after LPS), despite
a biphasic and sustained increase of GH secretion in the same animals (2.4
8 +/- 0.39 ng/ml 2 h after LPS and 2.7 +/- 0.37 ng/ml 5 h after LPS vs 0.77
+/- 0.10 before LPS; Briard et al. 1998a). Western ligand blot analysis in
IGFBPs showed an early short-lasting increase in IGFBP-1 (188.8 +/- 39% P<
0.05, 3 h after LPS). No significant change was seen for either IGFBP-2, -3
or -4. We observed a marked and sustained increase in cortisol (128.18 +/-
7.21 ng/ml 3 h after LPS, vs 21.17 +/- 4.22 before LPS). Insulin also incr
eased (27.69 +/- 3.90 mu U/ml 3 h after LPS, vs 13.48 +/- 1.69 before LPS)
and its burst coincided with that of IGFBP-1.
Moderately decreased IGF-I and increased IGFBP-1 plasma levels contrasted w
ith the sustained increase in GH secretion that we recently described, ther
eby suggesting that endotoxin causes a state of resistance to GH. This may
be exacerbated by reduced IGF-I bioavailability and/or action, and which ma
y participate in the pathophysiology of the catabolic state seen in sepsis.
The temporal analysis of hormone responses suggests that endotoxin-induced
alterations of the IGF-I/IGFBPs system may involve the prolonged and subst
antial somatostatin rise that we recently demonstrated, together with an in
crease in glucocorticoid and cytokine as more generally assumed.