Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, United Kingdom.
J Clin Endocrinol Metab. 2010 Apr;95(4):1898-908. doi: 10.1210/jc.2009-2071. Epub 2010 Feb 19.
Polymorphisms in genes involved in regulation, biosynthesis, metabolism, and actions of testicular sex hormones may influence hormone balance and phenotype of aging men.
We investigated the relationships between polymorphisms in genes related to pituitary-testicular endocrine function and health status.
Using cross-sectional baseline data, we conducted a multinational prospective cohort observational study consisting of a population survey of community-dwelling men.
A total of 2748 men, aged 40-79 (mean +/- sd, 60.2 + 11.2) yr, were randomly recruited from eight European centers. Forty-three polymorphisms were genotyped in the following genes: androgen receptor (AR), estrogen receptor-alpha and -beta (ESR1 and ESR2), steroid 5alpha-reductase type II (SRD5A2), 17alpha-hydroxylase/17,20-lyase (CYP17A1), aromatase (CYP19A1), sex hormone-binding globulin (SHBG), LH beta-subunit (LHB), and LH receptor (LHCGR).
We measured the associations between gene polymorphisms and endocrine, metabolic, and phenotypic parameters related to aging and sex hormone action.
Several polymorphisms in SHBG, ESR2, AR, CYP19A1, and LHB were significantly associated with circulating levels of SHBG, LH, total, free, and bioavailable testosterone and estradiol, the LH x testosterone product, and indices of insulin sensitivity. Apart from several previously reported associations between genes affecting estrogen levels and heel ultrasound parameters, no associations existed between polymorphisms and nonhormonal variables (anthropometry, blood lipids, blood pressure, hemoglobin, prostate symptoms, prostate-specific antigen, sexual dysfunction, cognition).
In aging men, polymorphisms in genes related to the pituitary-testicular endocrine function significantly influence circulating LH, testosterone, and estradiol levels, but the downstream effects may be too small to influence secondary phenotypic parameters.
参与调节、生物合成、代谢和作用的睾丸性激素的基因多态性可能会影响激素平衡和衰老男性的表型。
我们研究了与垂体-睾丸内分泌功能相关的基因多态性与健康状况之间的关系。
我们使用横断面基线数据进行了一项多中心前瞻性队列观察研究，该研究由社区居住男性的人群调查组成。
共有 2748 名年龄在 40-79 岁（平均值 +/- 标准差，60.2+11.2）岁的男性，随机从 8 个欧洲中心招募。共对雄激素受体（AR）、雌激素受体-α和-β（ESR1 和 ESR2）、类固醇 5α-还原酶 2 型（SRD5A2）、17α-羟化酶/17、20-裂合酶（CYP17A1）、芳香化酶（CYP19A1）、性激素结合球蛋白（SHBG）、LHβ亚基（LHB）和 LH 受体（LHCGR）中的 43 个基因多态性进行了基因分型。
我们测量了基因多态性与衰老和性激素作用相关的内分泌、代谢和表型参数之间的关系。
SHBG、ESR2、AR、CYP19A1 和 LHB 中的几个多态性与 SHBG、LH、总、游离和生物可利用睾酮和雌二醇、LH x 睾酮产物以及胰岛素敏感性指数相关。除了先前报道的几个影响雌激素水平的基因与脚跟超声参数之间的关联外，多态性与非激素变量（人体测量、血脂、血压、血红蛋白、前列腺症状、前列腺特异性抗原、性功能障碍、认知）之间不存在关联。
在衰老男性中，与垂体-睾丸内分泌功能相关的基因多态性显著影响循环 LH、睾酮和雌二醇水平，但下游影响可能太小，无法影响次要表型参数。
