Guido M, Romualdi D, Suriano R, Giuliani M, Costantini B, Apa R, Lanzone A
Department of Obstetrics and Gynecology, Università Cattolica del Sacro Cuore, Largo A.Gemelli 8, 00168 Roma, Italy.
Hum Reprod. 2004 Mar;19(3):534-9. doi: 10.1093/humrep/deh145. Epub 2004 Feb 12.
To investigate the effect of pioglitazone on adrenal steroidogenesis in polycystic ovary syndrome (PCOS), we studied 11 obese (two with BMI >25 kg/m(2); nine with BMI >27 kg/m(2)) PCOS women before and after 6 months of treatment at a dose of 45 mg/day.
During the early follicular phase, ultrasonography and hormonal assays were performed. On separate days, all women underwent an oral glucose tolerance test (OGTT), a euglycaemic hyperinsulinaemic clamp and an adrenocorticotrophin hormone (ACTH) test. The same protocol was repeated after therapy.
Pioglitazone treatment significantly reduced the insulin response to OGTT and improved the insulin sensitivity indices (P < 0.01 and P = 0.03 respectively). A significant decrease was found in LH (P < 0.05) and androstenedione (P < 0.01) levels after therapy, whereas the other hormonal parameters improved but not significantly. Pioglitazone administration reduced the response of 17alpha-hydroxyprogesterone (17OHP) and androstenedione to ACTH (P < 0.01 and P < 0.02 respectively), most likely through an inhibition of cytochrome P450. The same treatment was able to rebalance the relative activity of 17,20-lyase, as documented by an increase in the androstenedione:17OHP ratio (P < 0.05) after ACTH stimulation.
Our data support the contention that insulin enhances ACTH-stimulated steroidogenesis, while inducing a relative impairment of 17,20-lyase activity. Whether the beneficial effects of pioglitazone on this imbalance could be related to the ameliorated glyco-insulinaemic metabolism or to a direct effect on the adrenal glands remains to be determined.
为研究吡格列酮对多囊卵巢综合征（PCOS）患者肾上腺类固醇生成的影响，我们对11名肥胖的PCOS女性（2名BMI>25kg/m²；9名BMI>27kg/m²）进行了研究，这些患者接受了为期6个月、每日剂量45mg的治疗，观察治疗前后的变化。
在卵泡早期，进行超声检查和激素测定。在不同日期，所有女性均接受口服葡萄糖耐量试验（OGTT）、正常血糖高胰岛素钳夹试验和促肾上腺皮质激素（ACTH）试验。治疗后重复相同方案。
吡格列酮治疗显著降低了对OGTT的胰岛素反应，并改善了胰岛素敏感性指标（分别为P<0.01和P=0.03）。治疗后LH（P<0.05）和雄烯二酮（P<0.01）水平显著降低，而其他激素参数有所改善但不显著。吡格列酮给药降低了17α-羟孕酮（17OHP）和雄烯二酮对ACTH的反应（分别为P<0.01和P<0.02），最可能是通过抑制细胞色素P450。同样的治疗能够重新平衡17,20-裂解酶的相对活性，ACTH刺激后雄烯二酮：17OHP比值增加证明了这一点（P<0.05）。
我们的数据支持以下观点，即胰岛素增强ACTH刺激的类固醇生成，同时导致17,20-裂解酶活性相对受损。吡格列酮对这种失衡的有益作用是否与改善糖-胰岛素代谢或对肾上腺的直接作用有关，仍有待确定。
