Perfluorinated
iodine alkanes (PFIs) are used widely in the organic
fluorine industry. Increased production of PFIs has caused environmental
health concerns. To evaluate the potential endocrine-disrupting effect
of PFIs, we investigated the effects of perfluorooctyl iodide (PFOI)
on steroidogenesis in human adrenocortical carcinoma cells (H295R).
Levels of aldosterone, cortisol, 17β-estradiol, and testosterone
were measured in H295R culture medium upon treatment with perfluorooctanoic
acid (PFOA) and PFIs. Expression of 10 steroidogenic genes (<i>StAR</i>, <i>HMGR</i>, <i>CYP11A1</i>, <i>3βHSD2</i>, <i>17βHSD</i>, <i>CYP17</i>, <i>CYP21</i>, <i>CYP11B1</i>, <i>CYP11B2</i>, and <i>CYP19</i>) was measured by real-time polymerase
chain reaction. Levels of cyclic adenosine monophosphate (cAMP) and
adenylate cyclase (AC) activity were measured to understand the underlying
mechanism of steroidogenic perturbations. Levels of production of
aldosterone, cortisol, and 17β-estradiol were elevated significantly,
and the level of testosterone generation decreased upon treatment
with 100 μM PFOI. Similar to the effect induced by forskolin
(AC activator), expression of all 10 genes involved in the synthesis
of steroid hormones was upregulated significantly upon exposure to
100 μM PFOI. PFOA had no effect on steroid hormone production
or steroidogenic gene expression even though it is highly structurally
similar with PFOI. Therefore, the terminal -CF<sub>2</sub>I group
in PFOI could be a critical factor for mediation of steroidogenesis.
PFOI increased AC activity and cAMP levels in H295R cells, which implied
an underlying mechanism for the disturbance of steroidogenesis. These
data suggest that PFOI may act as an AC activator, thereby stimulating
steroidogenesis by activating a cAMP signaling pathway
