多囊卵巢综合征患者对ACTH反应的差异及其机制探讨
徐呈;杨军;张惠杰;洪洁;宁光;李小英
【期刊名称】《中华内分泌代谢杂志》 【年(卷),期】2010(026)005
【摘要】目的 观察多囊卵巢综合征(PCOS)患者ACTH兴奋试验后17羟孕酮(17OHP)的不同反应,及其与21羟化酶(CYP21)启动子区单核苷酸多态性的关系,初步探讨PCOS患者肾上腺源性高雄激素的产生机制.方法 对30名正常女性和101例PCOS患者进行ACTH兴奋试验,将PCOS患者分为高反应组(HR-PCOS)和正常反应组(NR-PCOS).比较两亚组基本情况、激素水平.对其中87例PCOS患者和30名正常女性进行CYP21启动子区-710 bp-1 bp测序,了解其单核苷酸多态性与ACTH兴奋后17OHP水平之间的关系.结果 在101例PCOS患者中,21例(20.8%)ACTH兴奋试验后17OHP水平高于正常,为HR-PCOS组;其余80例(79.2%)反应正常,为NR-PCOS组.HR-PCOS组血清总睾酮水平高于NR-PCOS组(P<0.05),NR-PCOS组高于对照组(P<0.01).HR-PCOS组基础17OHP、硫酸脱氢表雄酮(DHEAS)和兴奋后17OHP、DHEAS均显著高于NR-PCOS组和对照组(均P<0.05),NR-PCOS组与对照组之间没有差异.CYP21启动子区-535 C>T与17OHP高反应有关,-535位点的基因型与兴奋后170HP水平存在较好的相关性(r=0.20,P=0.03).其少见基因型(T/T型)和等位基因型T在高反应组中多见(P<0.05或P<0.01).该位点等位基因存在T者,发生17OHP高反应的相对危险度为3.69(95%CI 1.69～8.06).结论 约有20%PCOS患者ACTH兴奋试验后17OHP反应增高,并伴有血清总睾酮、肾上腺源性雄激素增高,提示PCOS患者17OHP对ACTH兴奋试验的高反应可能是
肾上腺源性高雄激素产生的机制之一.CYP21A2启动子区-535位点的基因变异与17OHP对ACTH兴奋试验的反应性有关.%Objective To explore the potential mechanism of adrenal androgen excess in patients with polycystic ovary syndrome (PCOS), ACTH stimulation test was conducted and the polymorphisms in the promoter region of CYP21 A2 gene were screened to verify the variations related to the responsiveness to ACTH stimulation. Methods 30 healthy women and 101 PCOS patients, matched for age, were recruited from Ruijin hospital. Blood biochemical examinations were taken and sex hormone profiles obtained at baseline. 17 hydroxyprogesterone( 17OHP)was measured at 0 and 60 min in an ACTH stimulation test. The -710 bp -1 bp of the promoter region of CYP21A2 was sequenced in 87 PCOS patients and 30 control subjects. Results According to the post-stimulation 17 OHP levels obtained from 30 healthy women,PCOS patients were allocated into one group with high responsiveness to ACTH ( HR-PCOS, n = 21) and the other with normal responsiveness to ACTH ( NR-PCOS, n = 80). Compared with NR-PCOS subjects, HR-PCOS patients had higher testosterone( P<0.05), basal and post-stimulation 17OHP (both P<0.01)and
dehydroepiandrosterone
sulfate
levels
(P<0.05
or
P<0.01) .whereas serum cortisol and androstenedione levels were not significantly different before and after ACTH stimulation test. The genotypes of locus -535 were well correlated with post-stimulation
17OHP levels (r = 0. 20,P = 0. 03) in PCOS patients and the control subjects. The genotype T/T or allele T was significantly more frequent in subjects with a higher fertile of post-stimulation 17OHP (P<0.05 or P<0. 01). The odds ratio(OR)for higher responsiveness to ACTH in women with allele T at -535 was 3. 69 (95% CI 1. 69-8. 06,P = 0. 000 7). Conclusions The PCOS patients with higher responsiveness to ACTH are characterized
by
severe
hyperandrogenemia
and
adrenal
androgenexcess,suggesting that adrenal androgen excess in some PCOS patients may be due to higher responsiveness to ACTH. The polymorphism of -535C>T in the promoter region of CYP21 A2 may play a role in regulating 21 hydroxylase gene expression and further influencing 17OHP responsiveness to ACTH. 【总页数】5页(359-363)
【关键词】多囊卵巢综合征;ACTH兴奋试验;17羟孕酮;21羟化酶;多态性,单核苷酸
【作者】徐呈;杨军;张惠杰;洪洁;宁光;李小英
【作者单位】200025,上海交通大学医学院附属瑞金医院内分泌代谢病科,上海市内分泌代谢病临床医学中心,上海市内分泌代谢病研究所;200025,上海交通大学医学院附属瑞金医院内分泌代谢病科,上海市内分泌代谢病临床医学中心,上海市内分泌代谢病研究所;200025,上海交通大学医学院附属瑞金医院内分泌代谢病科,上海市内分泌代谢病临床医学中心,上海市内分泌代谢病研究所;200025,上海交通大学医学院附属瑞金医院内分泌代谢病科,上海市内分泌代谢病临床医学
中心,上海市内分泌代谢病研究所;200025,上海交通大学医学院附属瑞金医院内分泌代谢病科,上海市内分泌代谢病临床医学中心,上海市内分泌代谢病研究所;200025,上海交通大学医学院附属瑞金医院内分泌代谢病科,上海市内分泌代谢病临床医学中心,上海市内分泌代谢病研究所 【正文语种】中文 【中图分类】 【文献来源】
https://www.zhangqiaokeyan.com/academic-journal-cn_chinese-journal-endocrinology-metabolism_thesis/0201232585228.html 【相关文献】
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多囊卵巢综合征患者对ACTH反应的差异及其机制探讨
