Carsia R V, Schwarz L A, Weber H
Proc Soc Exp Biol Med. 1987 Apr;184(4):461-7. doi: 10.3181/00379727-184-42502.
The neurotoxic agent, 3,3'-iminodiproprionitrile (IDPN), is a disrupter of neurofilament- and intermediate filament-organelle association. In the present study, the effect of IDPN on corticosteroidogenesis was investigated using isolated rat (having few intermediate filaments) and domestic fowl (having abundant intermediate filaments) adrenocortical cells. Cells were incubated with or without steroidogenic agents and precursors and with or without various concentrations of IDPN for 2 hr. IDPN had similar inhibitory potencies (as indicated by the half-maximal inhibitor concentrations (ID50 values] with both rat and domestic fowl cells despite their grossly different intermediate filament content. However, the average ID50 values of IDPN varied with the different steroidogenic agents and precursors used. The average IDPN ID50 values for maximal ACTH- and 8-bromo-cyclic AMP (8-Br-cAMP)-induced corticosterone production were equivalent (49.7 and 45.7 mM, respectively). However, the IDPN ID50 values for maximal ACTH-induced cAMP production, maximal 25-hydroxycholesterol- and pregnenolone-supported corticosterone production, and maximal ACTH- and 8-Br-cAMP-induced protein synthesis varied from 3.7 to 5.4 times the average ID50 values for maximal ACTH- and 8-Br-cAMP-induced corticosterone production. Thus, the inhibitory action of IDPN was not closely linked to the inhibition of ACTH-transmembrane signaling via cAMP, protein synthesis, and steroidogenic enzyme activity. The data suggest that IDPN inhibited corticosteroidogenesis at at a step after cAMP but before cholesterol side-chain cleavage and that the inhibition was not dependent on the presence of intermediate filaments.
神经毒性剂3,3'-亚氨基二丙腈（IDPN）是神经丝和中间丝与细胞器结合的破坏剂。在本研究中，使用分离的大鼠（中间丝较少）和家鸡（中间丝丰富）肾上腺皮质细胞研究了IDPN对皮质类固醇生成的影响。细胞在有或无类固醇生成剂和前体以及有或无不同浓度IDPN的情况下孵育2小时。尽管大鼠和家鸡细胞的中间丝含量差异很大，但IDPN对两者具有相似的抑制效力（以半数最大抑制剂浓度（ID50值）表示）。然而，IDPN的平均ID50值因所使用的不同类固醇生成剂和前体而异。最大促肾上腺皮质激素（ACTH）和8-溴环磷酸腺苷（8-Br-cAMP）诱导的皮质酮生成的IDPN平均ID50值相当（分别为49.7和45.7 mM）。然而，最大ACTH诱导的cAMP生成、最大25-羟胆固醇和孕烯醇酮支持的皮质酮生成以及最大ACTH和8-Br-cAMP诱导的蛋白质合成的IDPN ID50值是最大ACTH和8-Br-cAMP诱导的皮质酮生成的平均ID50值的3.7至5.4倍。因此，IDPN的抑制作用与通过cAMP、蛋白质合成和类固醇生成酶活性对ACTH跨膜信号传导的抑制没有密切联系。数据表明，IDPN在cAMP之后但在胆固醇侧链裂解之前的步骤抑制皮质类固醇生成，并且这种抑制不依赖于中间丝的存在。
