Steroid 11-beta-hydroxylase deficiency caused by compound heterozygosity for a novel mutation, p.G314R, in one CYP11B1 allele, and a chimeric CYP11B2/CYP11B1 in the other allele.

Aims: Steroid 11beta-hydroxylase deficiency (11beta-OHD) is the second most common (5-8%) cause of congenital adrenal hyperplasia (CAH), and results from homozygous or compound heterozygous mutations or deletions of the responsible gene CYP11B1. In order to better understand the molecular basis causing 11beta-OHD, we performed detailed studies of CYP11B1 in a newly described patient diagnosed with the classical signs of 11beta-OHD.

Methods: CYP11B1 of the patient was investigated by polymerase chain reaction (PCR), sequencing, restriction fragment length polymorphism (RFLP) analysis, Southern blotting, and transient cell expression.

Three repeats of CCCCTCC on the pyrimidine-rich sequence in the proximal 5' flanking region are required for efficient transcriptional activity of the human endothelial nitric oxide synthase gene.

The endothelial nitric-oxide synthase (eNOS) gene is constitutively expressed in endothelial cells, but numerous regulatory elements in the promoter region should contribute to the regulation for cell specific expression and the response to exogenous stimuli. A Sp1-binding consensus motif (-104 to -96) is essential for a core promoter activity of the human eNOS gene. In this study, we show that three repeats of CCCCTCC element (-74, -61, and -47), which located periodically at 13 and 14 nucleotide intervals on a pyrimidine-rich string in the proximal 5'-flanking region, were required for efficient transcriptional activity of the eNOS gene.

A novel nonsense mutation in the Cyp11B1 gene from a subject with the steroid 11beta-hydroxylase form of congenital adrenal hyperplasia.

11beta-Hydroxylase deficiency (11beta-OHD) inherited in an autosomal recessive manner accounts for about 5-8% of congenital adrenal hyperplasia (CAH). In order to clarify the underlying mechanism causing 11beta-OHD, we have done the molecular genetic analysis on the CYP11B1 gene in a patient diagnosed as 11beta-OHD. The nucleotide sequence of the patient's CYP11B1 revealed a novel nonsense mutation that converts codon 265 CAG (glutamine) to TAG (stop) of exon 4.

A missense mutation (GGC[435Gly]-->AGC[Ser]) in exon 8 of the CYP11B2 gene inherited in Japanese patients with congenital hypoaldosteronism.

Objectives: To clarify the underlying molecular mechanism of corticosterone methyl oxidase type II (CMO II) deficiency, Japanese patients newly diagnosed with CMO II deficiency were investigated.

Methods: We analyzed the patients' genomic DNA sequence on all 9 exons of the CYP11B2 gene. In addition, restriction fragment length polymorphism (RFLP) analysis and expression studies were performed.

Estrogen deficiency results in enhanced expression of Smoothened of the Hedgehog signaling in the thymus and affects thymocyte development.

Aromatase is an essential enzyme for estrogen synthesis. We investigated the role of estrogen in thymocyte development using aromatase-deficient (ArKO) mice. Like its role as a regulator of bone metabolism through regulating osteoprotegerin (OPG) production, estrogen is involved in the processes of thymocyte development although aromatase mRNA was not detectable in the thymus.

Dietary bisphenol A prevents ovarian degeneration and bone loss in female mice lacking the aromatase gene (Cyp19 ).

We previously generated mice lacking aromatase activity by targeted disruption of Cyp19 (ArKO mice), and reported phenotypes of the female mice, showing hemorrhage formation and follicular depletion in the ovary, diminution in uterine size, and bone loss. In the present study, we examined the influence of dietary bisphenol A (BPA), a monomer used for the production of polycarbonate and known to have estrogenic activity, on these phenotypes of the ArKO mice. When ArKO mice were fed chow diets supplemented with 0.

Aromatase-deficient (ArKO) mice are retrieved from severe hepatic steatosis by peroxisome proliferator administration.

Tamoxifen is a potent antagonist of estrogen, and hepatic steatosis is a frequent complication in adjuvant tamoxifen for breast cancer. Recently, aromatase-deficient (ArKO, Ar-/-) mice lacking intrinsic estrogen was developed and the molecular mechanism involved in progression of massive hepatic steatosis in estrogen-deficiency was elucidated; impairment in hepatic fatty acid beta-oxidation of peroxisomes, microsomes and mitochondria. This impairment is latent, but is potentially serious, because hepatic energy supply depends greatly on fatty acid beta-oxidation.