Cell-specific and hormonal regulation of the rat kidney androgen-regulated protein (KAP) gene

Abstract

In mouse kidney, the kidney androgen-regulated protein (KAP) gene is regulated in a sex-dependent manner by a complex tissue- and cell-specific multihormonal system. KAP is also found in mouse uterus during the period surrounding birth. We describe here for the first time the existence of KAP in a species other than mouse. The rat cDNA sequence was determined and the derived peptide sequence displayed only 53% identity with murine KAP, although the genomic organization of the genes was identical. Expression of rat KAP was restricted to kidney and uterus, but was constitutive in the latter and drastically induced at parturition. The renal expression of the rat KAP gene was sexually dimorphic and regulated by physiological levels of steroid hormones. The effects of castration, hypophysectomy, thyroidectomy, and castration plus thyroidectomy on KAP mRNA levels in both kidney and uterus were determined. Constitutive expression of the protein was strictly dependent on thyroid hormone in female kidneys where it was modulated by estrogens and other ovarian factor(s). In the uterus, KAP mRNA was mainly under estrogen control. In males, expression of the KAP gene was under the dual regulation of thyroid hormone and androgens. Its complex regulation suggests a carefully delineated role for KAP in the kidney and uterus, but its physiological function remains unknown.