Influence of thyroid hormones on the human ATP synthase beta-subunit gene promoter.

The action of thyroid hormones on the expression of the mitochondrial ATP synthase beta-subunit gene (ATPsyn beta) is controversial. We detected a binding site for the thyroid hormone receptor between -366 and -380 in the human ATPsyn beta gene by DNase I footprint analysis and band-shift assays. However, expression vectors in which the chloramphenicol acetyl transferase (CAT) reporter gene is driven by the 5' upstream region of ATPsyn beta gene were unresponsive to T3 when transiently transfected to HepG2 or GH4C1 cells. CAT constructs driven by the rat phosphoenolpyruvate carboxykinase (PEPCK) or the growth hormone (GH) promoters were stimulated several fold by T3 in parallel experiments. It is proposed that the biological effects of thyroid hormones on the ATPsyn beta expression occur through indirect mechanisms.