Wang Ling, Wang Yu-Dong, Wang Wen-Jun, Zhu Ying, Li Da-Jin
Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China.
J Mol Endocrinol. 2007 Apr;38(4):467-79. doi: 10.1677/jme.1.02173.
Dehydroepiandrosterone (DHEA) may be a promising agent for postmenopausal osteoporosis (PMO), but its mechanism to modulate osteoblasts (OBs) is yet to be explained. To elucidate the effects of DHEA treatment on the ovariectomized (OVX) mice and its mechanisms, we evaluated the morphology of mice bone tissue and expression of proliferating cell nuclear antigen (PCNA) in the vertebrae-derived OB after having treated the OVX animals with DHEA. The results showed that DHEA administration increased the expression of PCNA in OB and changed the bone tissue morphometry of the PMO model. To further investigate this mechanism, the OB was isolated from neonatal mice calvariae by the enzyme-digested assay, exposed to DHEA, and then analyzed for ultrastructure, DNA content, early apoptotic cells, and phosphorylation of extracellular signal-regulated kinase 1/2. It was found that DHEA promoted proliferation and inhibited apoptosis of OB significantly, via mitogen-activated protein kinase signaling pathway independent of either androgen receptor or estrogen receptor, suggesting that it may exert roles via a DHEA-specific receptor directly, not by way of conversion to androgens or estrogens.
脱氢表雄酮（DHEA）可能是治疗绝经后骨质疏松症（PMO）的一种有前景的药物，但其调节成骨细胞（OBs）的机制尚待阐明。为了阐明DHEA治疗对去卵巢（OVX）小鼠的影响及其机制，我们在用DHEA处理OVX动物后，评估了小鼠骨组织的形态以及椎骨来源的OB中增殖细胞核抗原（PCNA）的表达。结果表明，给予DHEA可增加OB中PCNA的表达，并改变PMO模型的骨组织形态计量学。为了进一步研究该机制，通过酶消化法从新生小鼠颅骨中分离出OB，使其暴露于DHEA，然后分析其超微结构、DNA含量、早期凋亡细胞以及细胞外信号调节激酶1/2的磷酸化情况。结果发现，DHEA通过丝裂原活化蛋白激酶信号通路显著促进OB的增殖并抑制其凋亡，该通路独立于雄激素受体或雌激素受体，这表明它可能直接通过DHEA特异性受体发挥作用，而不是通过转化为雄激素或雌激素来发挥作用。
