Pallardy M, Biola A
INSERM U461, Faculté de Pharmacie Paris-Sud, rue J.-B. Clément, Châtenay-Malabry.
C R Seances Soc Biol Fil. 1998;192(6):1051-63.
Glucocorticoids are physiological molecules that are also extensively used in clinics as anti-inflammatory, immunosuppressive or anti-tumoral agents. Glucocorticoids can induce apoptosis on normal lymphoid cells and play a key role in the physiology of thymic selection. In clinics these molecules are also used for their potencies in inducing apoptosis of malignant lymphoid cells. Glucocorticoids are mediating their effects after binding to an intracellular receptor belonging to the steroid receptor superfamily: the glucocorticoid receptor (GR). Once activated, the GR, can mediate his effects through direct binding on the DNA or via protein/protein interactions with transcription factors. Depending on the type of lymphocytes, the mechanism of apoptosis induced by glucocorticoids fall roughly in two categories: induction of "death genes" by the activated GR (I kappa B, c-jun) or repression of survival factors (AP-1, c-Myc). In the case of thymic selection the mechanism is more subtle depending on the mutual repression of Nur77 and GR.
糖皮质激素是一种生理分子，在临床上也被广泛用作抗炎、免疫抑制或抗肿瘤药物。糖皮质激素可诱导正常淋巴细胞凋亡，并在胸腺选择的生理过程中起关键作用。在临床上，这些分子还因其诱导恶性淋巴细胞凋亡的能力而被使用。糖皮质激素在与属于类固醇受体超家族的细胞内受体——糖皮质激素受体（GR）结合后发挥其作用。一旦被激活，GR可通过直接结合DNA或通过与转录因子的蛋白质/蛋白质相互作用来介导其效应。根据淋巴细胞的类型，糖皮质激素诱导凋亡的机制大致可分为两类：激活的GR诱导“死亡基因”（IκB、c-jun）或抑制生存因子（AP-1、c-Myc）。在胸腺选择的情况下，机制更为微妙，取决于Nur77和GR的相互抑制。
