Effect of octreotide on circulating IGF-I chromatographic profile: evidence for an inhibitory action on the formation of the 150-kDa ternary complex.
OBJECTIVE
The increasing use in clinical practice of octreotide (a somatostatin analogue which inhibits the secretion of GH and other peptide hormones) led us to study the effects of this treatment on GH, insulin-like growth factors (IGF)-I and II and IGF-binding protein (IGFBP)-3, as well as on circulating IGFBP complexes in acromegalic patients.


METHODS
The circulating concentrations of GH, IGF-I, IGF-II and IGFBP-3 were measured in acromegalic patients before and after 3, 6, 9, and 12 months of treatment with octreotide (group I: n = 5), and compared with those found in a group of patients (group II) treated with bromocriptine (n = 3), cabergoline (n = 7) radiotherapy (n = 3) or surgical therapy (n = 2). In pools of serum obtained from patients treated with octreotide, dopaminergic drugs, surgery and radiation, before and after therapy, immunoreactive IGF-I and IGFBP-3 were also evaluated after Superdex 200 gel filtration in neutral conditions.


RESULTS
Before treatment, the concentration of IGF-I and IGFBP-3 were above the normal range in all patients, while IGF-II levels were slightly reduced. After treatment with octreotide, IGF-I (P = 0.004), IGF-II (P = 0.02) and IGFBP-3 (P < 0.001) were significantly reduced as compared to basal levels. In subjects of group II, only IGF-I concentration was significantly reduced by the treatment (P = 0.02), and a negative correlation between IGF-I and IGF-II concentrations was found (r = -0.58, P < 0.0001). After gel filtration immunoreactive IGF-I and IGFBP-3 were found in the 150-kDa mol.wt. region in serum obtained from untreated patients and from treated patients of group II, while in the serum of octreotide-treated patients the IGF-I and IGFBP-3 peaks were shifted to the 60-kDa mol.wt. region, thus suggesting that the acid-labile subunit of the 150-kDa complex was drastically reduced. Since the GH concentrations in groups I and II were similar (M +/- SEM; 13.8 +/- 7.4 and 21.2 +/- 10.6 mU/l respectively), the marked reduction in acid-labile subunit in the octreotide treated patients can be explained by a direct inhibitory effect of somatostatin on the subunit.


CONCLUSIONS
Octreotide exerts an inhibitory effect not only on IGF-I but also on IGF-II. The reduced formation of the 150-kDa complex probably causes an increased metabolic clearance rate of IGF peptides which can account for the reduced concentration of both IGFs after treatment with octreotide.
Barreca
A
A
Department of Endocrinology and Metabolism, University of Genova, Italy.
Cariola
G
G
Ponzani
P
P
Arvigo
M
M
Foppiani
L
L
Giordano
G
G
Minuto
F
F
D000172:Acromegaly / Q000097:blood / Q000188:drug therapy; D000328:Adult; D001971:Bromocriptine / Q000627:therapeutic use; D000077465:Cabergoline; D002352:Carrier Proteins / Q000097:blood; D004873:Ergolines / Q000627:therapeutic use; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D007335:Insulin-Like Growth Factor II / Q000032:analysis; D008875:Middle Aged; D015282:Octreotide / Q000494:pharmacology* / Q000627:therapeutic use
D002352:Carrier Proteins; D004873:Ergolines; D018969:Insulin-Like Growth Factor Binding Proteins; D001971:Bromocriptine; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D013006:Growth Hormone; D000077465:Cabergoline; D015282:Octreotide