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Gonadal sex determination is a complex genetic process by which an embryonic primordium is driven to form an ovary or a testis, which requires a delicate dosage balance involving many genes. Disruption in this molecular pathway can lead to differences of sex development (DSD). Although some genetic mechanisms leading to 46,XY DSD have been elucidated, little is known about copy-number variation (CNV) causing testicular or ovotesticular 46,XX DSD. We describe a 20-year natural history of a man with SRY -negative 46,XX who was born with atypical male external genitalia, aortic coarctation, and bilateral blepharophimosis-ptosis. The molecular study identified a de novo heterozygous 3-Mb 15q26.2 deletion, a gene-poor locus containing NR2F2 , which encodes the nuclear receptor COUP-TFII that is highly expressed in ovary and cardiac arteries. Immunohistochemistry confirmed the low COUP-TFII expression on his ovotestis tissue. Monosomy of 15q26.2, encompassing the NR2F2 gene, may act as a Z-factor regulating the male sex determination negatively. This finding supports a novel type of CNV resulting in DSD in an individual who developed male puberty spontaneously. [ABSTRACT FROM AUTHOR]

Obese men may present hypogonadothrofic hypogonadism, mainly related to higher insulinemia and aromatase activity. Our objectives were to evaluate the relationship of sex-hormones profiles and frequency of depressive symptoms in 43 obese men, in a cross-sectional study. They had 19–60 years, and body mass index 30–50 kg/m2. LH, total and free testosterone (TT and FT), estradiol (E2), sex hormone binding globulin, estradiol/total testosterone ratio (E2/T) were analyzed. Depressive symptoms were evaluated by “beck depression inventory” (BDI), and significant depression was considered if BDI ≥ 16.Thirty-four (80%) presented low TT levels, but only 4 (14%) had low free testosterone and hypogonadism symptoms; 12 of 43 (28%) presented increased E2. Forty five (56%) presented depressive symptoms, but 16 (28% of the 45) had significant depression. BDI correlated positively with E2(r = 0.407;p = 0.001) and E2/T (r = 0.473;p = 0.001), but not TT or FT. Patients with significant depressive showed higher levels of estradiol (136 ± 48 versus 103 ± 48 pg/ml,p = 0.02) andE2/T(16.0 ± 9.9 versus 9.8 ± 4.6;p = 0.002) (mean ± SD).In conclusion, obese men may present relatively excess of estradiol and deficiency in testosterone, leading to an imbalance between these two hormones. The greater this imbalance, the more depressive symptoms had our patients. [ABSTRACT FROM PUBLISHER]

Individuals with Turner syndrome (TS) have increased risk for autoimmune diseases, especially thyroid abnormalities. The function of the vitamin D receptor ( VDR) gene is influenced by several genetic polymorphisms which are associated with a susceptibility to a range of autoimmune diseases. Thus, we have hypothesized a possible relationship between thyroid abnormalities and VDR polymorphisms ( ApaI/G1025-49T, TaqI/T1056C, FokI/T2C and BsmI G1024 ++ 283A) in TS patients. A case-control study was performed comprising 101 Brazilian women with TS and a control group consisting of 133 healthy fertile women without a history of autoimmune diseases. In TS group, 21.8% had Hashimoto's thyroiditis. Detection of VDR polymorphisms was performed using TaqMan system by real-time PCR. The χ2 was used to compare allele and genotype frequencies between groups. Combined genotypes of VDR gene polymorphisms were assessed by the haplotype analysis. A p value <0.05 was considered statistically significant. Relatively similar VDR polymorphisms genotype and allelic frequencies in cases and controls were found, even when only considering the patients with thyroid abnormalities. Haplotype analysis showed that none of the VDR haplotypes were associated to thyroid diseases in TS patients. In conclusion, the results showed no association between VDR gene polymorphisms and thyroid abnormalities in Brazilian TS patients tested. [ABSTRACT FROM AUTHOR]

OBJECTIVEThe frequency of gonadoblastoma is high in patients with Turner's syndrome bearing cells with Y or partial Y-chromosome. About 60% of patients with Turner's syndrome have a 45,X karyotype. In 30% of them a Y-sequence is disclosed by DNA analysis. To identify patients at risk of developing gonadoblastoma, a PCR based assay with SRY, ZFY and DYZ3 specific primers was carried out to detect different Y-sequences in the DNA of peripheral lymphocytes from patients with Turner's syndrome. DESIGN AND PATIENTSPeripheral blood karyotypes from 36 patients with Turner's syndrome were studied. Patients with proven Y-chromosomal material were excluded. Genomic DNA was extracted from peripheral blood. SRY and ZFY genes and DYZ3 repetion of Y-chromosome were amplified by PCR. Patients with clinical signs of hyperandrogenism or with positive Y-sequences by PCR underwent gonadectomy. The gonadal tissues were examined for Y-sequences using PCR, morphology and immunohistochemical study. MEASUREMENTSTurner's syndrome and signs of hyperandrogenism were evaluated both clinically and through laboratory tests. Haematoxylin and eosin staining was employed in gonadal morphology studies. The presence of testosterone was detected by immunohistochemistry using a monoclonal antibody. RESULTSTwo patients who had Y-positive blood samples and three hyperandrogenic (2 hirsutes, 1 virilized) Y-negatives underwent gonadectomy. PCR was carried out on their gonadal tissue. The tissue from the two patients without hyperandrogenism was Y-positive. The gonadal tissue from the three hyperandrogenics was Y-negative. Gonadal morphology disclosed hilus cell hyperplasia in the 3 hyperandrogenic Y-negatives and in one Y-positive patient; stromal luteoma and hyperthecosis in the virilized patient, cystadenofibroma in one hirsute patient and gonadoblastoma in one Y-positive. Testosterone was detected immunohistochemically in the hilus cell hyperplasia, stromal luteoma and... [ABSTRACT FROM AUTHOR]