Lifelong Excess in GH Elicits Sexually Dimorphic Effects on Skeletal Morphology and Bone Mechanical Properties.
Lifelong Excess in GH Elicits Sexually Dimorphic Effects on Skeletal Morphology and Bone Mechanical Properties.
复制标题
DOI：
10.1002/jbmr.4699
复制
发表时间：
2022-11
影响因子：
6.2
通讯作者：
Yakar, Shoshana
中科院分区：
文献类型：
--
作者：
Dixit, Manisha;Louis, Leeann D.;Basta-Pljakic, Jelena;Yildirim, Gozde;Poudel, Sher-Bahadur;Kumararaja, Fancy;List, Edward O.;Duran, Silvana Ortiz;Kopchick, John J.;Ruff, Ryan R.;Schaffler, Mitchell B.;Yakar, Shoshana
关键词：
肢端肥大症患者的生长激素(GH)水平过高与骨折的增加有关。尽管骨骼较宽，而且与骨矿物质密度无关，但仍会发生这种情况。我们利用牛生长激素(BGH)转基因小鼠，在血清和组织中显示GH和胰岛素样生长因子-1(IGF-1)的结构性过量，以研究GH和IGF-1终身增加对骨骼完整性的影响。此外，我们将酸性不稳定亚单位(ALS)零(ALSKO)基因与BGH小鼠杂交，以降低血清IGF-1水平。我们的发现表明生长激素对皮质骨和松质骨的性别二型性影响。雄性BGH小鼠表现出皮质直径增大，但骨髓腔扩张，皮质变薄，血管孔隙率增加，这与骨干强度和硬度的降低有关。相比之下，雌性BGH小鼠表现出明显较小的骨干直径，较大的皮质骨厚度和轻微的组织弹性模数(通过微压痕)，最终导致总体上更强壮、更坚硬的骨骼。我们发现血清中I型胶原的C末端端肽和前胶原1N前肽增加，与循环IGF-1水平无关，表明随着GH的过量，骨重建增加。在松质骨室，特别是在股骨远端干骺端，也观察到了对过量生长激素反应的性别二型性。雌性BGH小鼠在衰老过程中保持其骨小梁结构，而雄性BGH小鼠的骨小梁体积显著减少，并与骨小梁变薄有关。我们的结论是，病理性的生长激素过量导致骨结构的性别二型性改变和骨量的增加，这影响了整个骨的力学性质，以及骨材料性质的性别差异。
Excess in growth hormone (GH) levels, seen in patients with acromegaly, is associated with increases in fractures. This happens despite wider bones and independent of bone mineral density. We used the bovine GH (bGH) transgenic mice, which show constitutive excess in GH and insulin-like growth factor-1 (IGF-1) in serum and tissues, to study how lifelong increases in GH and IGF-1 affect skeletal integrity. Additionally, we crossed the acid labile subunit (ALS) null (ALSKO) to the bGH mice, to reduce serum IGF-1 levels. Our findings indicate sexual dimorphic effects of GH on cortical and trabecular bone. Male bGH mice showed enlarged cortical diameters, but with marrow cavity expansion and thin cortices as well as increased vascular porosity that were associated with reductions in diaphyseal strength and stiffness. In contrast, female bGH mice presented with significantly smaller diameter diaphysis, with greater cortical bone thickness and with a slightly reduced tissue elastic modulus (by micro indentation), ultimately resulting in overall stronger, stiffer bones. We found increases in C-terminal telopeptide of type 1 collagen and pro-collagen type 1 N pro-peptide in serum, independent of circulating IGF-1 levels, indicating increased bone remodeling with excess GH. Sexual dimorphism in response to excess GH was also observed in the trabecular bone compartment, particularly at the femur distal metaphysis. Female bGH mice preserved their trabecular architecture during aging, while trabecular bone volume in male bGH mice significantly reduced and associated with thinning of the trabeculae. We conclude that pathological excess in GH results in sexual dimorphic changes in bone architecture and gains in bone mass, that affect whole-bone mechanical properties, as well as a sex-specific differences in bone material properties.
登录
查看更多内容
影响因子：
5.8
作者：
Mazziotti, Gherardo;Bianchi, Antonio;Giustina, Andrea
通讯作者：
Giustina, Andrea
影响因子：
5.8
作者：
Malgo, F.;Hamdy, N. A. T.;Appelman-Dijkstra, N. M.
通讯作者：
Appelman-Dijkstra, N. M.
影响因子：
4.8
作者：
Liu, Zhongbo;Han, Tianzhen;Yakar, Shoshana
通讯作者：
Yakar, Shoshana
影响因子：
3.7
作者：
Maffezzoni, Filippo;Maddalo, Michele;Giustina, Andrea
通讯作者：
Giustina, Andrea
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y