MacGillivray M H, Morishima A, Conte F, Grumbach M, Smith E P
Department of Pediatrics, School of Medicine & Biomedical Sciences, State University of New York at Buffalo, Children's Hospital of Buffalo, 14222, USA.
Horm Res. 1998;49 Suppl 1:2-8. doi: 10.1159/000053061.
The goals of this presentation are to review the essential roles of aromatase, estrogens and the estrogen receptor in pubertal growth. Estrogen deficiency due to mutations in the aromatase gene (CYP19) and estrogen resistance due to disruptive mutations in the estrogen receptor gene have no effect on normal male sexual maturation in puberty. However, they lead to absence of the pubertal growth spurt, delayed bone maturation, unfused epiphyses, continued growth into adulthood and very tall adult stature in both sexes. Gonadotropin and androgen levels are elevated in patients with either estrogen deficiency (aromatase deficiency) or estrogen resistance (estrogen receptor mutation). Glucose intolerance, hyperinsulinemia and lipid abnormalities are also present. Skeletal integrity is compromised. Increased bone turnover, reduced bone mineral density and osteoporosis develop in both sexes. Sexual orientation is appropriate in males and females. In females, aromatase deficiency in the ovary causes pubertal virilization and multicystic ovaries because of elevated gonadotropins and androgens. Simultaneously, secondary sexual maturation fails to occur. Placental aromatase deficiency results in virilization of the mother and her female fetus because of the accumulation of potent androgens which are not converted to estrogens. The male fetus has normal genitalia. In conclusion, estrogens are essential for normal female secondary sexual maturation, bone maturation, epiphyseal fusion, pubertal growth spurt and achievement of normal bone mineral mass. Estrogens also influence insulin sensitivity and lipid homeostasis. However, estrogens do not appear to be essential for fetal survival, placental growth, or female sexual differentiation.
本报告的目的是回顾芳香化酶、雌激素和雌激素受体在青春期生长中的重要作用。芳香化酶基因（CYP19）突变导致的雌激素缺乏以及雌激素受体基因破坏性突变导致的雌激素抵抗对青春期正常男性性成熟没有影响。然而，它们会导致青春期生长突增缺失、骨成熟延迟、骨骺未融合、持续生长至成年以及两性成年后身材异常高大。雌激素缺乏（芳香化酶缺乏）或雌激素抵抗（雌激素受体突变）患者的促性腺激素和雄激素水平升高。同时还存在葡萄糖不耐受、高胰岛素血症和脂质异常。骨骼完整性受到损害。两性均出现骨转换增加、骨矿物质密度降低和骨质疏松。男性和女性的性取向正常。在女性中，卵巢芳香化酶缺乏会导致青春期男性化和多囊卵巢，原因是促性腺激素和雄激素水平升高。同时，第二性征成熟无法发生。胎盘芳香化酶缺乏会导致母亲及其女性胎儿男性化，因为强效雄激素积累而未转化为雌激素。男性胎儿生殖器正常。总之，雌激素对于正常女性第二性征成熟、骨成熟、骨骺融合、青春期生长突增以及达到正常骨矿物质质量至关重要。雌激素还影响胰岛素敏感性和脂质稳态。然而，雌激素似乎对于胎儿存活、胎盘生长或女性性别分化并非必不可少。
