Van Der Eerden B C J, Van De Ven J, Lowik C W G M, Wit J M, Karperien M
Department of Pediatrics, Leiden University Medical Center, The Netherlands.
Endocrinology. 2002 Oct;143(10):4048-55. doi: 10.1210/en.2002-220093.
To assess whether growth plate-specific production of sex steroids is possible, we have surveyed the presence of several key-enzymes involved in androgen and estrogen metabolism in the tibial growth plate of female and male rats during development. Using in situ hybridization, mRNAs of aromatase p450, type I and II 17beta-hydroxysteroid dehydrogenase (HSD), steroid sulfatase (STS), and 5alpha-reductase were detected in proliferating and hypertrophic chondrocytes of the growth plate. The former three were strongly up-regulated around sexual maturation (7 wk), whereas the latter two were expressed at a relatively constant level during development. These data were supported by measuring aromatase, type I 17beta-HSD, and STS enzyme activities in chondrocytes collected from tibial growth plates at 1 and 7 wk of age. Of the enzymes studied, there were minor differences between the sexes in aromatase and 5alpha-reductase expression only. In conclusion, our findings clearly indicate the presence of various enzymes involved in sex steroid metabolism in the tibial growth plate, especially in sexually maturing rats, a timepoint at which sex steroids have major effects on longitudinal growth. Our data suggest that intracrinology in the rat growth plate can occur and may be a major source of local sex steroid delivery.
为评估生长板是否可能特异性产生性类固醇,我们调查了雌性和雄性大鼠发育过程中胫骨生长板中参与雄激素和雌激素代谢的几种关键酶的存在情况。利用原位杂交技术,在生长板的增殖和肥大软骨细胞中检测到了芳香化酶p450、Ⅰ型和Ⅱ型17β-羟基类固醇脱氢酶(HSD)、类固醇硫酸酯酶(STS)和5α-还原酶的mRNA。前三种酶在性成熟(7周)左右强烈上调,而后两种酶在发育过程中表达水平相对恒定。通过测量1周龄和7周龄大鼠胫骨生长板软骨细胞中的芳香化酶、Ⅰ型17β-HSD和STS酶活性,这些数据得到了支持。在所研究的酶中,仅芳香化酶和5α-还原酶的表达在性别之间存在微小差异。总之,我们的研究结果清楚地表明,胫骨生长板中存在参与性类固醇代谢的各种酶,尤其是在性成熟的大鼠中,此时性类固醇对纵向生长有重大影响。我们的数据表明,大鼠生长板中可能发生内分泌学现象,并且可能是局部性类固醇递送的主要来源。