Studies of a co-chaperone of the androgen receptor, FKBP52, as candidate for hypospadias

BACKGROUND: Hypospadias is a common inborn error of the male urethral development, for which the aetiology is still elusive. Polymorphic variants in genes involved in the masculinisation of male genitalia, such as the androgen receptor, have been associated with some cases of hypospadias. Co-regulators of the androgen receptor start being acknowledged as possible candidates for hormone-resistance instances, which could account for hypospadias. One such molecule, the protein FKBP52, coded by the FKBP4 gene, has an important physiological role in up-regulating androgen receptor activity, an essential step in the development of the male external genitalia. The presence of hypospadias in mice lacking fkbp52 encouraged us to study the sequence and the expression of FKBP4 in boys with isolated hypospadias. PATIENTS AND METHODS: The expression of FKBP52 in the genital skin of boys with hypospadias and in healthy controls was tested by immunohistochemistry. Mutation screening in the FKBF4 gene was performed in ninety-one boys with non syndromic hypospadias. Additionally, two polymorphisms were typed in a larger cohort. RESULTS: Immunohistochemistry shows epithelial expression of FKBP52 in the epidermis of the penile skin. No apparent difference in the FKBP52 expression was detected in healthy controls, mild or severe hypospadias patients. No sequence variants in the FKBP4 gene have implicated in hypospadias in our study. CONCLUSION: FKBP52 is likely to play a role in growth and development of the male genitalia, since it is expressed in the genital skin of prepubertal boys; however alterations in the sequence and in the expression of the FKBP4 gene are not a common cause of non-syndromic hypospadias

Testicular Dysgenesis Syndrome and the Estrogen Hypothesis: A Quantitative Meta-Analysis

BACKGROUND: Male reproductive tract abnormalities such as hypospadias and cryptorchidism, and testicular cancer have been proposed to comprise a common syndrome together with impaired spermatogenesis with a common etiology resulting from the disruption of gonadal development during fetal life, the testicular dysgenesis syndrome (TDS). The hypothesis that in utero exposure to estrogenic agents could induce these disorders was first proposed in 1993. The only quantitative summary estimate of the association between prenatal exposure to estrogenic agents and testicular cancer was published over 10 years ago, and other systematic reviews of the association between estrogenic compounds, other than the potent pharmaceutical estrogen diethylstilbestrol (DES), and TDS end points have remained inconclusive. OBJECTIVES: We conducted a quantitative meta-analysis of the association between the end points related to TDS and prenatal exposure to estrogenic agents. Inclusion in this analysis was based on mechanistic criteria, and the plausibility of an estrogen receptor (ER)-–mediated mode of action was specifically explored. RESULTS: We included in this meta-analysis eight studies investigating the etiology of hypospadias and/or cryptorchidism that had not been identified in previous systematic reviews. Four additional studies of pharmaceutical estrogens yielded a statistically significant updated summary estimate for testicular cancer. CONCLUSIONS: The doubling of the risk ratios for all three end points investigated after DES exposure is consistent with a shared etiology and the TDS hypothesis but does not constitute evidence of an estrogenic mode of action. Results of the subset analyses point to the existence of unidentified sources of heterogeneity between studies or within the study population

Biological Activity and Chemical Composition of Hydrodistilled and Supercritical Extracts of Xanthium strumarium L. Leaves

The antimicrobial and antioxidant activities and the composition of the essential oil and of the supercritical extracts of Xanthium strumarium were studied. The best yields were observed in the supercritical extracts (SFE). The composition of the extracts obtained by SFE and by hydrodistillation presented little qualitative difference, but they did differ quantitatively. The essential oil contained a high content of beta-guaiene (79.6%) while as the major compounds in the supercritical extracts were unidentifiable compound with Kovats Index of 2303 and xanthinin. All the X. strumarium extracts showed strong antimicrobial activity against Staphylococcus aureus, Escherichia coli, Salmonella thyphimurium, Pseudomonas aeruginosa and Clostridium perfringens, however no differences were observed between the extracts. Poor antioxidant activity was found for all the Xanthium strumarium extracts.22542442