Bogazzi Fausto, Ultimieri Federica, Raggi Francesco, Russo Dania, Manetti Luca, Cosci Chiara, Sardella Chiara, Costa Aurelio, Santini Ferruccio, Locci Teresa, Bartalena Luigi, Martino Enio
Department of Endocrinology, University of Pisa, Italy.
Clin Endocrinol (Oxf). 2007 Jan;66(1):7-12. doi: 10.1111/j.1365-2265.2006.02675.x.
Obesity is a clinical feature of patients with Cushing's disease. Peroxisome proliferators-activated receptor (PPAR)gamma is the master regulator of adipogenesis; however, the expression of PPARgamma isoforms in the subcutaneous adipose tissue (SAT) of patients with Cushing's disease is unknown.
The expression of PPARgamma1 and PPARgamma2 was evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence (PPARgamma2 only) in SAT samples of 7 patients with untreated active Cushing's disease (Cushing(UNTR)), 8 with Cushing's disease in remission (Cushing(REM)) after pituitary adenomectomy, 15 normal lean subjects (Control(LEAN)), and 15 obese patients (Control(OBE)).
Control(LEAN) had a higher degree of PPARgamma1 than PPARgamma2 (PPARgamma2/PPARgamma1 ratio, 0.55 +/- 0.35). PPARgamma2/PPARgamma1 ratio decreased in Cushing(UNTR) (0.10 +/- 0.043, P < 0.03 vs. Control(LEAN) and Control(OBE)), because of either increased PPARgamma1 or reduced PPARgamma2 expression. PPARgamma2/PPARgamma1 ratio was 0.48 +/- 0.07 in Cushing(REM) patients (P < 0.04 vs. Cushing(UNTR), P < 0.03 vs. Control(OBE)). PPARgamma2/PPARgamma1 ratio was higher in Control(OBE) 0.90 +/- 0.38 than in Control(LEAN) (P < 0.005 vs. Control(LEAN), P < 0.03 vs. Cushing(REM), P < 0.009 vs. Cushing(UNTR)). PPARgamma2/PPARgamma1 ratio was related to serum cortisol levels only in patients with Cushing'disease (r = 0.688, P < 0.02).
Cushing(UNTR) patients had an abnormal expression of PPARgamma isoforms in SAT related to serum cortisol levels. Although further studies are necessary, it is conceivable that variations in the expression of PPARgamma isoforms might have a role in the abnormal adipogenesis of patients with Cushing's disease.
肥胖是库欣病患者的临床特征。过氧化物酶体增殖物激活受体（PPAR）γ是脂肪生成的主要调节因子；然而，库欣病患者皮下脂肪组织（SAT）中PPARγ亚型的表达尚不清楚。
通过实时逆转录聚合酶链反应（RT-PCR）和免疫荧光法（仅检测PPARγ2）评估7例未经治疗的活动性库欣病患者（库欣病（未治疗组））、8例垂体腺瘤切除术后处于缓解期的库欣病患者（库欣病（缓解组））、15例正常瘦人（对照组（瘦人））和15例肥胖患者（对照组（肥胖者））的SAT样本中PPARγ1和PPARγ2的表达。
对照组（瘦人）中PPARγ1的表达程度高于PPARγ2（PPARγ2/PPARγ1比值为0.55±0.35）。库欣病（未治疗组）中PPARγ2/PPARγ1比值降低（0.10±0.043，与对照组（瘦人）和对照组（肥胖者）相比，P<0.03），原因是PPARγ1表达增加或PPARγ2表达降低。库欣病（缓解组）患者的PPARγ2/PPARγ1比值为0.48±0.07（与库欣病（未治疗组）相比，P<0.04；与对照组（肥胖者）相比，P<0.03）。对照组（肥胖者）的PPARγ2/PPARγ1比值（0.90±0.38）高于对照组（瘦人）（与对照组（瘦人）相比，P<0.005；与库欣病（缓解组）相比，P<0.03；与库欣病（未治疗组）相比，P<0.009）。仅在库欣病患者中，PPARγ2/PPARγ1比值与血清皮质醇水平相关（r=0.688，P<0.02）。
库欣病（未治疗组）患者SAT中PPARγ亚型的表达异常，且与血清皮质醇水平相关。尽管有必要进行进一步研究，但可以设想PPARγ亚型表达的变化可能在库欣病患者异常的脂肪生成中起作用。
