Endocrine Disruption in Human Placenta: Expression of the Dioxin-Inducible Enzyme, Cyp1a1, Is Correlated With That of Thyroid Hormone-Regulated Genes: The Journal of Clinical Endocrinology & Metabolism: Vol 0, No 0

Context:

Thyroid hormone (TH) is essential for normal development; therefore, disruption
of TH action by a number of industrial chemicals is critical to
identify. Several chemicals including polychlorinated biphenyls are
metabolized by the dioxin-inducible enzyme CYP1A1; some of their
metabolites can interact with the TH receptor. In animals, this
mechanism is reflected by a strong correlation between the expression of
CYP1A1 mRNA and TH-regulated mRNAs. If this mechanism occurs in humans,
we expect that CYP1A1 expression will be positively correlated with the
expression of genes regulated by TH.

Objective:

The objective of the study was to test the hypothesis that CYP1A1 mRNA
expression is correlated with TH-regulated mRNAs in human placenta.

Methods:

One hundred sixty-four placental samples from pregnancies with no thyroid
disease were obtained from the GESTE study (Sherbrooke, Qéubec, Canada).
Maternal and cord blood TH levels were measured at birth. The mRNA
levels of CYP1A1 and placental TH receptor targets [placental lactogen
(PL) and GH-V] were quantitated by quantitative PCR.

Results:

CYP1A1 mRNA abundance varied 5-fold across 132 placental samples that had
detectable CYP1A1 mRNA. CYP1A1 mRNA was positively correlated with PL (r = 0.64; P < .0001) and GH-V (P < .0001, r = 0.62) mRNA. PL and GH-V mRNA were correlated with each other (r = 0.95; P < .0001), suggesting a common activator. The mRNAs not regulated by TH were not correlated with CYP1A1 expression.

Conclusions:

CYP1A1 mRNA expression is strongly associated with the expression of
TH-regulated target gene mRNAs in human placenta, consistent with the
endocrine-disrupting action of metabolites produced by CYP1A1.