Cell Biology and Toxicology

, Volume 10, Issue 1, pp 35–43 | Cite as

Modulation of adrenal cell functions by cadmium salts: 3. Sites affected by CdCl2 during stimulated steroid synthesis

  • O. P. Mgbonyebi
  • C. T. Smothers
  • J. J. Mrotek


In previous studies cadmium chloride (CdCl2) nonlethally inhibited Y-1 mouse adrenal tumor cell 20-dihydroxyprogesterone (20DHP) secretion, affecting unstimulated and stimulated steroidogenic pathway sites differently. In addition, dibutyryl cAMP-stimulated 20DHP secretion was unaffected by CdCl2, while the site of the unstimulated effect was indirectly shown to involve steps between endogenous cholesterol utilization and 20-hydroxycholesterol association with mitochondrial cytochrome P450 side-chain cleavage enzyme. In the present study we determined CdCl2 effects on plasma membrane sites preceding pre-dbcAMP-stimulation of 20DHP secretion. Y-1 cells were incubated 0.5 h in medium with or without cadmium (using the concentration that inhibited adrenocorticotropin- (ACTH)-stimulated steroid secretion by 50%) together with exogenously added maximally stimulating concentrations of ACTH, cholera toxin, forskolin, or adenosine triphosphate Cholera toxin, forskolin and ATP bypass specific plasma membrane sites involved in the synthesis of intracellular cAMP and activate the steroid hormone biosynthetic pathway. Cadmium effects on ACTH-stimulated endogenous cAMP secretion were also examined. CdCl2 significantly reduced Y-1 cell 20DHP secretion following exposure to ACTH, cholera toxin, forskolin, and ATP; it also significantly decreased endogenous cAMP secretion into culture medium. These data may be interpreted to suggest that CdCl2 altered Y-1 cell regulation of adenyl cyclase activity, which reduced cAMP-activated cholesterol uptake by mitochondria as a consequence.


cadmium chloride stimulated corticosteroid secretion Y-1 adrenal cells 





adenosine triphosphate


analysis of variance

CdCl2 or Cd2+

cadmium chloride


cyclic 3′,5′-adenosine monophosphate


cholera toxin


dibutyryl cAMP,N′,O′-dibutyryl-3′,5′-adenosine monophosphate


ethylene glycol bis tetraacetic acid


serum-free Eagle's Minimum Essential Medium with all other supplements




N-2-hydroxyethylpiperazine-N-1,2-ethanesulfonic acid


concentration inhibiting stimulated steroid secretion by 50%


international unit


Eagle's Minimum Essential Medium


cytochrome P450 side-chain cleavage enzyme






standard error of the mean


serum-containing Eagle's Minimum Essential Medium with supplements




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Copyright information

© Kluwer Academic Publishers 1994

Authors and Affiliations

  • O. P. Mgbonyebi
    • 1
  • C. T. Smothers
    • 1
  • J. J. Mrotek
    • 1
  1. 1.Physiology DepartmentMeharry Medical CollegeNashvilleUSA

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