Department of Pediatrics, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea.
Department of Nuclear Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea.
J Korean Med Sci. 2020 Nov 23;35(45):e370. doi: 10.3346/jkms.2020.35.e370.
Estrogen controls the pubertal growth spurt, growth plate closure, and accretion of bone mineral density (BMD) of long bones after biding estrogen receptor (ER). There are two subtypes of ER, ERα and ERβ. If each ER subtype has different effects, we may control those actions by manipulating the estrogen binding intensity to each ER subtype and increase the final adult height without markedly reducing BMD or impairing reproductive functions. The purpose of our study was to compare these effects of ERα and ERβ on long bones in ovariectomized rats.
Thirty female rats were ovariectomized and randomly divided into 3 groups. The control, propylpyrazole triol (PPT), and 2,3-bis (4-hydroxyphenyl) propionitrile (DPN) groups were subcutaneously injected for 5 weeks with sesame oil, PPT as an ERα agonist, and DPN as an ERβ agonist, respectively. The crown-lump length and body weight were measured weekly. BMD, serum levels of growth hormone (GH) and estradiol were checked before and after 5 weeks of injections. Pituitary expression levels were determined with quantitative real-time polymerase chain reaction, the proximal tibias were dissected, decalcified and stained with hematoxylin-eosin, and the thicknesses of epiphyseal plates including proliferative and hypertrophic zones were measured in 20-evenly divided sites after 5 weeks of injections. Comparisons for auxological data, serum hormone and pituitary expression levels, BMD, and epiphyseal plate thicknesses among 3 groups before and after injections were conducted.
There was no significant difference in body lengths among 3 groups. The body weights were significantly lower, but, serum GH, pituitary expression levels, and BMDs were higher in PPT group than the other 2 groups after 5 weeks of injections. There was no significant difference in the thicknesses of the total epiphyseal plate, proliferative, and hypertrophic zone among 3 groups.
ERα is more involved in pituitary GH secretion and bone mineral deposition than ERβ. Weight gain might be prevented with the ERα agonist.
雌激素通过结合雌激素受体(ER)控制青春期生长突增、生长板闭合以及长骨骨密度(BMD)的增加。ER 有两种亚型,ERα 和 ERβ。如果每种 ER 亚型都有不同的作用,我们可以通过操纵雌激素与每种 ER 亚型的结合强度来控制这些作用,从而增加最终的成年身高,而不会显著降低 BMD 或损害生殖功能。我们研究的目的是比较 ERα 和 ERβ 对去卵巢大鼠长骨的这些影响。
30 只雌性大鼠被卵巢切除,并随机分为 3 组。对照组、丙基吡唑三醇(PPT)和 2,3-双(4-羟苯基)丙腈(DPN)组分别皮下注射 5 周芝麻油、PPT(ERα 激动剂)和 DPN(ERβ 激动剂)。每周测量冠-结节长度和体重。注射前和注射后 5 周检测 BMD、血清生长激素(GH)和雌二醇水平。用定量实时聚合酶链反应测定垂体表达水平,注射后 5 周解剖并脱钙,苏木精-伊红染色,测量 20 个均匀划分部位的骺板厚度。比较 3 组注射前后的生长数据、血清激素和垂体表达水平、BMD 和骺板厚度。
3 组间体长无显著差异。注射后 5 周,PPT 组体重明显低于其他 2 组,但血清 GH、垂体表达水平和 BMD 较高。3 组总骺板、增殖和肥大区厚度无显著差异。
ERα 比 ERβ更多地参与垂体 GH 分泌和骨矿物质沉积。ERα 激动剂可能预防体重增加。