It is clear that the expression of the selected genes (TCF-20, WT1, ZNF621, and THRB), which were identified for the first time in this work as putative PPAR-responsive genes, was altered in the presence of the used agents (Table 2) and that among them TCF-20 was affected the most by EFA-CLA.
To our knowledge, we proposed several new genes that could be potentially PPAR-regulated: BCAR3, LZTS, SLC5A, TCF20, WT1, ZNF621, and THRB (transcript TR[beta]2) (Table 2).
Available literature addresses the relationship between receptors encoded by PPAR and THRB genes [48-50].
Simultaneously, cis9,trans11 isomer upregulated THRB suppressor and downregulated WT1 oncogene showing a small part of a PPAR action that in case of EFA-CLA leads to the observed reduction in proliferation of the breast cancer cells.
The mutant THRB molecules have either a reduced affinity for [T.sub.3] or an impaired interaction with one of the cofactors involved in the mediation of thyroid hormone action.
The THRA gene is expressed in cardiac and skeletal tissues, THRB splice variant 1 is expressed in brain, liver, and kidney, and THRB splice variant 2 is expressed in the hypothalamus and the pituitary.
 Human genes: THRB, thyroid hormone receptor, beta; THRA, thyroid hormone receptor, alpha.
Leey and Cryer (1) nicely discuss a patient with a heterozygous mutation in the THRB gene and review the differential diagnosis.
Conversely, Thrb and Gsr were induced exclusively in 2-ppm-exposed animals compared with 5 ppm, suggesting a toxic response specific to the lower dose of [O.sub.3].
The 5-fold induction in the expression of thyroid hormone receptor Thrb and 5- to 15-fold suppression in IGF-binding protein are the first observations of O3-induced alterations in thyroid hormone receptor expression and regulation of Igfbp2.
The observation of differential expression of Igfbp2 and Thrb provides the first biochemical clue for their involvement in [O.sub.3] toxicity and its exacerbation in hyperthyroid conditions.