Hazum E, Schvartz I
Biochem Biophys Res Commun. 1984 Dec 14;125(2):532-8. doi: 10.1016/0006-291x(84)90572-2.
Gonadotropin releasing hormone (GnRH), preincubated with cultured rat pituitary cells, induced down regulation of GnRH receptors in a time- and dose-dependent manner. The specific binding was inhibited by 50% after 30 min and maximal inhibition (70%) was obtained after 75 min preincubation with 1 microM GnRH. Preincubation of the cells for 2 h with 10 nM GnRH inhibited the specific binding by 20%, reaching a plateau of 70% inhibition with 0.1 microM GnRH. Concomitantly, exposure of the cells to GnRH caused a time- and dose-dependent desensitization of LH release. The responsiveness of the desensitized cells was not parallel to the binding capacity and was inhibited to a greater extent (93%). Photoactivation of GnRH receptors with iodinated [azidobenzoyl-D-Lys6]GnRH in control and desensitized cells resulted in the identification of a single specific band with the same apparent molecular weight of 60K daltons. These results indicate that structural alterations of GnRH receptors are not associated with GnRH-induced desensitization. Therefore, desensitization may involve conformational changes in the receptor or more likely a post-receptor mechanism.
与培养的大鼠垂体细胞预孵育的促性腺激素释放激素（GnRH），以时间和剂量依赖的方式诱导GnRH受体下调。与1μM GnRH预孵育30分钟后，特异性结合被抑制50%，预孵育75分钟后获得最大抑制（70%）。用10 nM GnRH将细胞预孵育2小时，特异性结合被抑制20%，用0.1μM GnRH时达到70%抑制的平台期。同时，将细胞暴露于GnRH会导致LH释放的时间和剂量依赖性脱敏。脱敏细胞的反应性与结合能力不平行，且受到更大程度的抑制（93%）。在对照细胞和脱敏细胞中，用碘化的[叠氮苯甲酰-D-赖氨酸6]GnRH对GnRH受体进行光活化，结果鉴定出一条单一的特异性条带，其表观分子量相同，均为60千道尔顿。这些结果表明，GnRH受体的结构改变与GnRH诱导的脱敏无关。因此，脱敏可能涉及受体的构象变化，或者更可能是受体后机制。
