Effect of 3,3'-iminodiproprionitrile (IDPN) on corticosteroidogenesis of isolated adrenocortical cells.
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.
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D002645:Chickens; D003345:Corticosterone / Q000096:biosynthesis; D000242:Cyclic AMP / Q000378:metabolism; D006888:Hydroxycholesterols / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009570:Nitriles / Q000494:pharmacology*; D011284:Pregnenolone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012741:Sexual Maturation
D000305:Adrenal Cortex Hormones; D006888:Hydroxycholesterols; D009570:Nitriles; D015124:8-Bromo Cyclic Adenosine Monophosphate; C008110:3,3'-iminodipropionitrile; D011284:Pregnenolone; C007997:25-hydroxycholesterol; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D003345:Corticosterone