Chagin Andrei S, Sävendahl Lars
Pediatric Endocrinology Unit, Department of Woman and Child Health, Karolinska Institute, SE-171 76 Stockholm, Sweden.
J Clin Endocrinol Metab. 2007 Dec;92(12):4873-7. doi: 10.1210/jc.2007-0814. Epub 2007 Sep 18.
Our objective was to study whether GPR30 is expressed in the epiphyseal growth plate and its potential role as a modulator of pubertal growth.
Estrogens play a crucial role in the regulation of skeletal maturation and longitudinal bone growth. We have previously shown that both estrogen receptors (ERs) alpha and beta are expressed in the human epiphyseal growth plate. Recently, a membrane-bound ER referred to as GPR30 was discovered, but the role played by this receptor in the regulation of longitudinal bone growth is not yet known.
PATIENTS/METHODS: Biopsies were collected from the tibial growth plates of 14 boys and seven girls that underwent epiphyseal surgery to arrest longitudinal bone growth. The patients were in different stages of puberty and suffered from inequality in leg length or extreme tall stature. Paraffin-embedded sections of the growth plates were used to detect expression of the GPR30 protein.
The highest level of GPR30 expression was observed in hypertrophic chondrocytes, although cells with positive immunostaining were also detected in the resting zone. In contrast, no immunoreactivity was found in the proliferative zone. During pubertal progression there was a clear decline in the level of GPR30 expression in both boys and girls.
The novel ER GPR30 is expressed in the human growth plate, and the level of expression declines during pubertal progression. Although a relationship between GPR30 expression and age may underlie the observed pubertal decline in the GPR30 level, our observations suggest that this receptor could be involved in the modulation of longitudinal bone growth during puberty.
我们的目的是研究GPR30是否在骨骺生长板中表达及其作为青春期生长调节因子的潜在作用。
雌激素在骨骼成熟和纵向骨生长的调节中起关键作用。我们之前已经表明雌激素受体(ERs)α和β均在人类骨骺生长板中表达。最近,发现了一种称为GPR30的膜结合型ER,但该受体在纵向骨生长调节中所起的作用尚不清楚。
患者/方法:从14名男孩和7名女孩的胫骨生长板获取活检组织,这些患者接受了骨骺手术以阻止纵向骨生长。患者处于青春期的不同阶段,患有腿长不等或身材极高的问题。生长板的石蜡包埋切片用于检测GPR30蛋白的表达。
在肥大软骨细胞中观察到GPR30表达水平最高,尽管在静止区也检测到免疫染色阳性的细胞。相比之下,增殖区未发现免疫反应性。在青春期进展过程中,男孩和女孩的GPR30表达水平均明显下降。
新型ER GPR30在人类生长板中表达,且在青春期进展过程中表达水平下降。尽管GPR30表达与年龄之间的关系可能是观察到的青春期GPR30水平下降的基础,但我们的观察结果表明该受体可能参与青春期纵向骨生长的调节。