Peroxisome Proliferator Activated Receptor {gamma} Expression Is Reduced in the Colonic Mucosa of Acromegalic Patients

Fausto Bogazzi, Federica Ultimieri, Francesco Raggi, Aurelio Costa, Maurizio Gasperi, Elisabetta Cecconi, Franco Mosca, Luigi Bartalena and Enio Martino

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){gamma}, 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{gamma} 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{gamma} mRNA was 15230 ± 891 transcripts. Patients with AcroUntr had 2750 ± 688 transcripts of PPAR{gamma}. (p < 0.0001) vs. Controls); patients AcroSMSa had 4629 ± 1286 transcripts of PPAR{gamma}. (p = NS vs AcroUntr, p = 0.0002 vs Controls); patients with AcroRem had 8261 ± 2481 transcripts of PPAR{gamma} (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{gamma} (r = 0.43, p = 0.03). In conclusion, patients with active Acro have a reduced expression of PPAR{gamma} 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.