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 PPARgamma 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 microg/l; IGF-I, 769 +/- 298 microg/l; AcroRem: GH, 1.0 +/- 1.3 microg/l; IGF-I, 248 +/- 96 microg/l; AcroSMSa: GH, 7.8 +/- 12 microg/l; IGF-I, 429 +/- 221 microg/l;
Controls: GH, 0.8 +/- 0.7 microg/l; IGF-I, 203 +/- 67 microg/l. In the CONTROLS the level of expression of PPARgamma mRNA was 15230 +/- 891 transcripts. Patients with AcroUntr had 2750 +/- 688 transcripts of PPARgamma. (p < 0.0001) vs. CONTROLS); patients AcroSMSa had 4629 +/- 1286 transcripts of PPARgamma. (p = NS vs AcroUntr, p = 0.0002 vs. CONTROLS); patients with AcroRem had 8261 +/- 2481 transcripts of PPARgamma (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 PPARgamma (r = 0.43, p = 0.03). In conclusion, patients with active Acro have a reduced expression of PPARgamma 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.