Effects of thyroid hormone on the androgenic expression of KAP gene in mouse kidney

Abstract

The kidney androgen-regulated protein (KAP) gene exhibits a cell-specific hormonal regulation of its expression in the epithelial cells of proximal tubules of mouse kidney, where T3 is required for constitutive expression in the straight segments and androgens for expression in the convoluted ones. By using different models of hypothyroidism, we demonstrate that maximal androgen-mediated induction of the gene depends on thyroid hormone as well. This constitutes a specific event, since vitamin D3 cannot mimic the effects of T3, albeit their remarkable functional relationship. It is also shown that while congenital hypothyroid hyt/hyt male mice, exposed to maternal T3 in the gestational period, exhibit diminished but existent androgen-dependent cortical responses, mice exposed to goitrogens during gestation and postnatally are unable to express the gene even at postnatal day ninety. Impairment of KAP cortical expression in hypothyroid animals does not correlate with lower levels of androgens or androgen receptor expression.