Schulster D, Rafferty B, Williams B
Mol Cell Endocrinol. 1984 Jun;36(1-2):43-51. doi: 10.1016/0303-7207(84)90083-2.
The characteristics of the sensitization and desensitization of superfused, rat dissociated adrenal fasciculata cells were examined. The dynamic output of steroids and cyclic AMP was determined following pulsed treatment with various agonists. Repeated doses of identical small amounts of ACTH or ACTH gave gradually increasing responses which were maximal after 3-4 injections, but then desensitized the adrenal cells. An initial dose of 2.5 X 10(-11) moles of ACTH, itself insufficient to stimulate steroidogenesis in this system, had the effect of priming the cells, which showed an enhanced initial response and achieved maximum responsiveness on the second injection of 4 X 10(-13) moles ACTH. Thereafter, although the cells exhibited a diminishing steroid output, a dose at the end of the experiment of 8 X 10(-12) moles ACTH restored the maximum responsiveness, and demonstrated that cell loss or death could not account for the desensitization effect. Only a sensitization of the cells was observed following repeated doses of 5 X 10(-6) moles cyclic AMP. Since no desensitization effect was discernible for this agonist, it was concluded that in this system the lesion giving rise to the desensitization effect occurred prior to the adenylate cyclase catalytic unit for the generation of cyclic AMP within the cell and the receptor-nucleotide-regulatory protein complex is thus implicated in the desensitization mechanism for adrenal steroidogenesis. The studies demonstrate the exquisite sensitivity of adrenal cells to the desensitizing effects of even brief intermittent pulses of ACTH.
对灌注的大鼠离体肾上腺束状带细胞致敏和脱敏的特性进行了研究。在用各种激动剂进行脉冲处理后，测定了类固醇和环磷酸腺苷（cAMP）的动态输出。重复给予相同小剂量的促肾上腺皮质激素（ACTH）会使反应逐渐增强，在3 - 4次注射后达到最大值，但随后肾上腺细胞会发生脱敏。初始剂量为2.5×10⁻¹¹摩尔的ACTH本身不足以刺激该系统中的类固醇生成，但具有使细胞致敏的作用，细胞在第二次注射4×10⁻¹³摩尔ACTH时显示出增强的初始反应并达到最大反应性。此后，尽管细胞的类固醇输出逐渐减少，但在实验结束时给予8×10⁻¹²摩尔ACTH的剂量可恢复最大反应性，这表明细胞丢失或死亡不能解释脱敏效应。重复给予5×10⁻⁶摩尔环磷酸腺苷后仅观察到细胞致敏。由于未观察到该激动剂的脱敏效应，因此得出结论，在该系统中，导致脱敏效应的损伤发生在细胞内生成环磷酸腺苷的腺苷酸环化酶催化单元之前，受体 - 核苷酸调节蛋白复合物因此参与了肾上腺类固醇生成的脱敏机制。这些研究证明了肾上腺细胞对即使是短暂间歇性脉冲的促肾上腺皮质激素脱敏作用具有极高的敏感性。
