Adult reproductive functions after early postnatal inhibition by imatinib of the two receptor tyrosine kinases, c-kit and PDGFR, in the rat testis
Adult reproductive functions after early postnatal inhibition by imatinib of the two receptor tyrosine kinases, c-kit and PDGFR, in the rat testis
复制标题
伊马替尼抑制大鼠睾丸中的两种受体酪氨酸激酶（c-kit和PDGFR）后的成年生殖功能
DOI：
10.1016/j.reprotox.2008.03.004
复制
发表时间：
2008-08-01
影响因子：
3.3
通讯作者：
Jahnukainen, Kirsi
中科院分区：
文献类型：
--
作者：
Nurmio, Mirja;Kallio, Jenny;Jahnukainen, Kirsi
甲磺酸伊马替尼（Glivec（R）STI 571; Novartis）是ATP的小分子类似物，其有效地抑制Bcr-Abl、PDGFR-α、PDGFR-β、c-Fms、Arg和c-kit的酪氨酸激酶活性，是引入癌症治疗的新型分子靶向剂之一。干细胞因子（SCF）/c-kit和血小板源性生长因子（PDGF）信号通路调控大鼠生后睾丸精原干细胞和间质细胞池的形成。研究了出生后短期暴露于伊马替尼对雄性大鼠及其后代生育力的影响。伊马替尼显著降低了给药动物的产仔数，并导致血清促性腺激素水平永久性轻微升高。睾丸形态和参与干细胞因子/c-kit和PDGF信号传导的配体和受体的mRNA水平恢复到对照水平，后代出生时健康。我们的研究结果表明，用某些分子靶向药物治疗癌症可能通过抑制特定的生理信号通路对睾丸发育产生潜在影响。(C)2008年爱思唯尔公司All rights reserved.
Imatinib mesylate (Glivec (R) STI 571; Novartis), a small-molecular analog of ATP that potently inhibits the tyrosine kinase activities of Bcr-Abl, PDGFR-alpha, PDGFR-beta, c-Fms, Arg and c-kit, is one of the novel molecularly targeted agents being introduced into cancer therapy. Stem cell factor (SCF)/c-kit and platelet-derived growth factor(PDGF) signaling pathways regulate postnatal formation of the pools of spermatogonial stem cells and Leydig cells in the rat testis. The effect of short postnatal imatinib exposure on fertility of the male rats and offspring of these animals were investigated. Imatinib significantly reduced the litter size sired by the treated animals and led to permanently slightly elevated serum levels of the gonadotropins. Testicular morphology and mRNA levels of ligands and receptors involved in stem cell factor/c-kit and PDGF signaling returned to control levels, and the offsprings were born healthy. Our findings indicate that treatment of cancer with certain molecularly targeted drugs may have latent effects on testicular development by inhibiting specific physiological signaling pathways. (C) 2008 Elsevier Inc. All rights reserved.