Ibáñez Lourdes, Marcos Maria Victoria, Potau Neus, White Carlie, Aston Christopher E, Witchel Selma Feldman
Endocrinology Unit, Hospital Sant Joan de Deu, University of Barcelona, Barcelona, Spain.
Fertil Steril. 2002 Dec;78(6):1288-93. doi: 10.1016/s0015-0282(02)04238-3.
To test the hypothesis that lower sex hormone-binding globulin (SHBG) concentrations are associated with heterozygosity for the G972R variant of the IRS-1 gene among adolescent girls with a history of precocious pubarche (PP) and hyperinsulinemic ovarian hyperandrogenism.Association study. Academic research environment. Adolescent girls with a history of PP and healthy adolescent female control subjects. Determine body mass index; measure serum androgen, insulin-like growth factor (IGF)-binding protein 1, lipids, IGF-1, and SHBG concentrations; perform glucose tolerance tests; and assay for G972R variant of the IRS-1 gene. Serum androgen, IGFBP-1, and SHBG concentrations; IRS-1 genotypes.Twenty-five of 54 (45%) girls with a history of PP developed hyperinsulinemic ovarian hyperandrogenism at adolescence. Frequency of heterozygosity for G972 was 31% among girls with a history of PP, 40% among girls with hyperinsulinemic ovarian hyperandrogenism, and 19% among healthy control subjects. Sex hormone-binding globulin concentrations were lower among girls heterozygous for G972R variant. Predictors of progression from PP to hyperinsulinemic ovarian hyperandrogenism included chronological age, insulin, low-density lipoprotein cholesterol, and IGFBP-1 concentrations. The low mean SHBG concentration found among G972R carriers suggests that this variant may be a minor locus associated with development of hyperinsulinemic insulin resistance and ovarian androgen excess in girls with a history of PP.
在有性早熟（PP）和高胰岛素血症性卵巢高雄激素血症病史的青春期女孩中，较低的性激素结合球蛋白（SHBG）浓度与胰岛素受体底物-1（IRS-1）基因G972R变异的杂合性相关。关联研究。学术研究环境。有PP病史的青春期女孩和健康的青春期女性对照受试者。测定体重指数；测量血清雄激素、胰岛素样生长因子（IGF）结合蛋白1、脂质、IGF-1和SHBG浓度；进行葡萄糖耐量试验；检测IRS-1基因的G972R变异。血清雄激素、IGFBP-1和SHBG浓度；IRS-1基因型。54名有PP病史的女孩中有25名（45%）在青春期发展为高胰岛素血症性卵巢高雄激素血症。有PP病史的女孩中G972杂合性频率为31%，高胰岛素血症性卵巢高雄激素血症女孩中为40%，健康对照受试者中为19%。G972R变异杂合的女孩中SHBG浓度较低。从PP进展为高胰岛素血症性卵巢高雄激素血症的预测因素包括实足年龄、胰岛素、低密度脂蛋白胆固醇和IGFBP-1浓度。在G972R携带者中发现的较低平均SHBG浓度表明，该变异可能是与有PP病史女孩的高胰岛素血症性胰岛素抵抗和卵巢雄激素过多发展相关的一个次要基因座。
