Ek I, Arner P, Bergqvist A, Carlström K, Wahrenberg H
Department of Medicine, Huddinge University Hospital, Karolinska Institute, Sweden.
J Clin Endocrinol Metab. 1997 Apr;82(4):1147-53. doi: 10.1210/jcem.82.4.3899.
The polycystic ovary syndrome (PCOS) is the most common hyperandrogenic disorder among women and is characterized by metabolic and cardiovascular aberrations similar to those seen in the so-called insulin resistance syndrome. The regulation of lipolysis was investigated in isolated abdominal sc adipocytes from 10 nonobese women with PCOS and in 11 age- and body mass index-matched healthy women. Eight PCOS women were reinvestigated after 3 months of treatment with combined oral contraceptives containing ethinyl estradiol and norethisterone, which normalized hyperandrogenicity. The PCOS women showed a marked resistance to the lipolytic effect of noradrenaline due to defects at two different levels in the lipolytic cascade: first, a 7-fold reduction in sensitivity to the beta 2-selective agonist terbutaline (P < 0.005), which could be ascribed to a 50% lower beta 2-adrenoceptor density (P < 0.02) as determined with radioligand binding; there was no difference with regard to dobutamine (beta 1) or clonidine (alpha 2-sensitivity) or beta 1-adrenoceptor density; second, the maximum lipolytic response was also 35% lower (P < 0.02) in the PCOS women compared to that in the healthy women. This was seen with all beta-adrenergic agonists and the postreceptor-acting agents forskolin (activating adenylyl cyclase) and dibutyryl cAMP (activating protein kinase). Neither beta 2-adrenoceptor sensitivity or density nor the reduced lipolytic responsiveness was restored by 3 months of oral contraceptives treatment. The results indicate the existence of a marked impairment of catecholamine-induced lipolysis in nonobese PCOS women displaying early features of the insulin resistance syndrome due to multiple lipolysis defects as a lower beta 2-adrenoceptor density and reduced function of the protein kinase, hormone-sensitive lipase complex. These lipolysis defects are identical to those observed in the insulin resistance (metabolic) syndrome and could be a primary pathogenic mechanism for the development of these disorders.
多囊卵巢综合征（PCOS）是女性中最常见的高雄激素血症疾病，其特征是存在与所谓胰岛素抵抗综合征中所见相似的代谢和心血管异常。对10名非肥胖PCOS女性以及11名年龄和体重指数相匹配的健康女性的分离腹部皮下脂肪细胞中的脂肪分解调节进行了研究。8名PCOS女性在接受含乙炔雌二醇和炔诺酮的复方口服避孕药治疗3个月后进行了再次研究，该治疗使高雄激素血症恢复正常。PCOS女性对去甲肾上腺素的脂解作用表现出明显抵抗，这是由于脂解级联反应中两个不同水平的缺陷所致：首先，对β2选择性激动剂特布他林的敏感性降低了7倍（P<0.005），这可归因于用放射性配体结合法测定的β2肾上腺素能受体密度降低了50%（P<0.02）；在多巴酚丁胺（β1）或可乐定（α2敏感性）或β1肾上腺素能受体密度方面没有差异；其次，与健康女性相比，PCOS女性的最大脂解反应也降低了35%（P<0.02）。在所有β肾上腺素能激动剂以及作用于受体后的药物福斯高林（激活腺苷酸环化酶）和二丁酰环磷腺苷（激活蛋白激酶）中均观察到这种情况。口服避孕药治疗3个月后，β2肾上腺素能受体敏感性或密度以及降低的脂解反应性均未恢复。结果表明，在表现出胰岛素抵抗综合征早期特征的非肥胖PCOS女性中，由于多种脂解缺陷，如β2肾上腺素能受体密度降低和蛋白激酶、激素敏感性脂肪酶复合物功能降低，儿茶酚胺诱导的脂肪分解存在明显损害。这些脂解缺陷与在胰岛素抵抗（代谢）综合征中观察到的缺陷相同，可能是这些疾病发生发展的主要致病机制。
