|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1997 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1996 : ¥1,300,000 (Direct Cost : ¥1,300,000)
Ad4BP (SF-1) is not only a steroidogenic tissue transcriptional factor but also be very essential for the development of a functioning hypothalamus-pituitary-adrenal and gonadal axis. We recently clarified a structure of human Ad4BP gene. Fom the deletion analysis of the 5'-flanking region of human Ad4BP gene, we clarified that E-box is very essential for the basal transcriptional activity of this gene, as also reported in other species. The Ad4BP-desrupted mouse was devoid of its normal adrenal glands and gonads as well as a selective loss of gonadotropin-specific markers in the pituitary. Recently, a new nuclear hormone receptor gene, DAX-1 was isolated from the Xp21 region and was shown to be fatally mutated in patients with X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HHG). We also identified some mutations in several such patients. However, the molecular basis of exceptional cases with AHC and HHG,such as female patients and patients with autosomal recessive inheritance remains unclear. In this respect, we analyzed the Ad4BP genes of three female patients who were clinically suspected to have AHC and HHG,but no mutations were found in all three cases. The result may suggest an existence of different autosomal gene responsible for this phenoytpe.