Schaison G
Service d'Endocrinologie et des maladies de la reproduction, Hôpital de Bicêtre, Le Kremlin Bicêtre.
Ann Endocrinol (Paris). 1989;50(3):200-7.
The mechanism of action of the antihormone substances, and more particularly of RU 486 antiprogesterone, is still poorly understood. The antagonist effect may take place at the receptor site while the latter is in its 8S inactive form. The antihormone blocks the heat shock protein 90 (HSP 90) and prevents the receptor from changing into its 4S active form, solely capable of binding the DNA-specific hormone responding element (HRE). However, if the antihormone does not impede receptor 4S activation, the antagonist effect may be explained by insufficient HRE affinity. Another possibility would be that the antihormone-4S receptor complex becomes chromatin-bound, although no bond is formed at the HRE-specific site. A certain affinity for HRE would explain the agonist effect of the antihormones. An affinity for DNA, outside HRE, would explain some specific activities peculiar to the antihormone. RU 486, which is both an antiprogesterone and an antiglucocorticoid substance, exhibits some powerful antagonistic characteristics. When neither progesterone nor cortisol is available, RU 486 displays weak agonistic effects. It can, therefore, serve as a good experimental model from which to study the mode of action of the antihormones.
抗激素物质，尤其是RU 486抗孕酮的作用机制仍未被充分了解。拮抗剂作用可能发生在受体处于8S无活性形式时的受体位点。抗激素阻断热休克蛋白90（HSP 90），并阻止受体转变为其4S活性形式，只有4S活性形式的受体才能与DNA特异性激素反应元件（HRE）结合。然而，如果抗激素不阻碍受体4S激活，拮抗剂作用可能是由于HRE亲和力不足。另一种可能性是抗激素-4S受体复合物与染色质结合，尽管在HRE特异性位点未形成结合。对HRE的一定亲和力可以解释抗激素的激动剂作用。在HRE之外对DNA的亲和力可以解释抗激素特有的一些特定活性。RU 486既是一种抗孕酮物质，也是一种抗糖皮质激素物质，具有一些强大的拮抗特性。当既没有孕酮也没有皮质醇时，RU 486表现出微弱的激动作用。因此，它可以作为研究抗激素作用模式的良好实验模型。
