Department of Endocrinology and Metabolism (F.B., F.U., F.R., M.G., E.C., E.M.), Department of Oncology and Transplantation (A.C., F.M.), University of Pisa, Pisa, Chair of Endocrinology, University of Insubria (L.B.), Varese, Italy
Abstract
Acromegalic patients have an increased prevalence of colonic
polyps, due to the elevated serum insulin like growth factor (IGF)-I
levels. The mechanisms underlying this process are poorly understood.
Peroxisome proliferator activated receptor (PPAR), a nuclear
receptor that regulates adipocyte differentiation, is highly expressed
in the human colonic mucosa, where it induces growth inhibition and
cell differentiation. In the present study we evaluated the expression
of PPAR
in the bioptic samples of colonic mucosa from 22 patients
with acromegaly (Acro) and 13 normal subjects (Controls) matched for
age and sex. Among Acro patients, 10 had active, untreated disease
(AcroUntr), 6 were in remission after surgery (AcroRem), and 6 had
active disease under treatment with somatostatin analogs (AcroSMSa).
Serum GH and IGF-I (mean ± SD) levels were as follows: AcroUntr: GH,
36 ± 40 µg/l; IGF-I, 769 ± 298 µg/l; AcroRem: GH, 1.0 ± 1.3
µg/l; IGF-I, 248 ± 96 µg/l; AcroSMSa: GH, 7.8 ± 12 µg/l; IGF-I,
429 ± 221 µg/l; Controls: GH, 0.8 ± 0.7 µg/l; IGF-I, 203 ± 67
µg/l. In the Controls the level of expression of PPAR
mRNA was
15230 ± 891 transcripts. Patients with AcroUntr had 2750 ± 688
transcripts of PPAR
. (p < 0.0001) vs. Controls); patients AcroSMSa
had 4629 ± 1286 transcripts of PPAR
. (p = NS vs AcroUntr, p =
0.0002 vs Controls); patients with AcroRem had 8261 ± 2481 transcripts
of PPAR
(p = 0.008 vs AcroUntr, p = NS vs AcroSMSa, p = 0.007 vs
Controls). A significant inverse correlation was found between serum
IGF-I concentrations and the level of expression of PPAR
(r = 0.43,
p = 0.03). In conclusion, patients with active Acro have a reduced
expression of PPAR
in the colonic mucosa, which appears be related
to the increased serum IGF-I levels and might lead to an increased
prevalence of colonic polyps.