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  • 1
    Electronic Resource
    Electronic Resource
    Immunohistochemistry and in situ hybridization of the androgen receptor in the developing human prostate (1998)
    Springer
    Anatomy and embryology 197 (1998), S. 199-208 
    Details
    ISSN: 1432-0568
    Keywords: Key words Human prostate ; Development ; Androgen receptor ; Immunohistochemistry ; In situ hybridization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  As it is suggested that the androgen receptor mechanism is required for prostatic development, we attempted to determine the appearance, expression and distribution of the androgen receptor in embryonic, infantile and pubertal human prostate. Using mono- and polyclonal antibodies and a digoxigenin-labeled 713 bp riboprobe, the androgen receptor expression in paraffin sections of fetal, infantile, and pubertal prostates was studied at the protein and RNA level. Under highly standardized conditions, application of the polyclonal antibodies resulted in a weak cytoplasmic and nuclear labeling of the epithelium of fetal glands. No immunoreaction was obtained with monoclonal antibodies. Applying the polyclonal antibody to pubertal and adult specimens, immunoreactivity of the androgen receptor was positive in nuclei of adluminal and basal epithelial cells, in interstitial and vascular smooth muscle cells and vascular endothelium, whereas ganglionic cells and enteroendocrine cells were negative. In situ hybridization with the digoxigenin-labeled riboprobe gave clear positive results already in epithelium of very young fetal specimens. A semiquantitative visual evaluation of in situ hybridizations showed that intermediate intensity of expression was increased in pubertal and adult specimens, whereas strong expression was reduced in prostatic epithelium. Conclusions: The essential findings are: (1) an early expression of androgen receptor mRNA in the fetal prostate; (2) no immunoreaction of monoclonal antibodies against the androgen receptor in the same specimens, (3) a decrease of androgen receptor mRNA expression, but increase in immunoreactivity of the androgen receptor protein with the onset of glandular maturation during puberty.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004290050131
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  • 2
    Electronic Resource
    Electronic Resource
    Molecular characterization of the androgen receptor gene in boys with hypospadias (1994)
    Springer
    European journal of pediatrics 153 (1994), S. 317-321 
    Details
    ISSN: 1432-1076
    Keywords: Androgen receptor, genetics ; Mutation ; Single strand conformation polymorphism ; Hypospadias: sexual development
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Development of male external genitalia is dependent on androgens, and karyotypic males lacking appropriate levels of androgens or functionally normal receptors may show abnormal virilization. Mutations in the androgen receptor gene cause abnormal receptor function and diverser mutations may be associated with heterogenous clinical signs of androgen insensitivity. In this study, we have searched for the existence of androgen receptor gene mutations carried by some patients with hypospadias. Genomic DNA samples from peripheral blood leucocytes from 21 patients with different degrees of hypospadias were studied. Analysis of the androgen receptor gene was performed by exon-specific amplification using polymerase chain reaction, single strand conformation polymorphism analysis, and direct genomic sequencing. Although a silent polymorphism was identified in exon 1 of the androgen receptor gene, the majority of patients studied (20/21) did not carry androgen receptor gene mutations. One patient with severe hypospadias and bilateral cryptorchidism was found to carry a point mutation in exon 8. We conclude that mutations in the androgen receptor gene may be carried by subset of patients with genital ambiguity presenting primarily with hypospadias, but this is not the underlying cause in the majority of cases. Characterization of this genetic defect may be important for classification and subsequent conservative therapeutic approaches for these patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01956409
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Molecular genetic analysis and human chorionic gonadotropin stimulation tests in the diagnosis of prepubertal patients with partial 5α-reductase deficiency (1996)
    Springer
    European journal of pediatrics 155 (1996), S. 445-451 
    Details
    ISSN: 1432-1076
    Keywords: Male pseudohermaphroditism ; Hypospadias ; 5α-Reductase 2 ; Single strand conformation polymorphism ; Human chorionic gonadotropin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Reduced conversion of testosterone (T) to dihydrotestosterone (DHT) results in defective virilization in karyotypic males. Different mutations in the 5α-reductase type 2 gene cause the phenotypic variability of the disease. In this report we describe four prepubertal patients with a predominantly male phenotype who carry homozygous point mutations in the 5α-reductase type 2 gene and address the specific T and DHT response to different human chorionic gonadotropin (hCG) stimulation tests. For molecular genetic analysis, DNA from peripheral blood leucocytes was studied. The coding region of the 5α-reductase type 2 gene was characterized by exon-specific polymerase chain reaction amplification, non-radioactive single strand polymorphism analysis, and direct sequencing. Three different homozygous point mutations (Gly196−Ser, Arg227−Gln and Ala228−Thr) were identified in the patients. In contrast, in the DNA from 100 phenotypically normal males only two heterozygous abnormalities (Ile196−Ile, ΔMet157) were characterized. For hormonal studies, T and DHT were measured in serum before and after hCG stimulation employing different protocols. HCG stimulation with 5000 IU/m2 once and prolonged stimulation with seven injections of 1500 IU hCG per single dose every other day were used. Conclusion While abnormal T/DHT ratios were identified with both hCG protocols in the patients, prolonged stimulation lead to higher T values and to higher T/DHT ratios, and hence to a better discrimination of pathologic results.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01955179
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    Paper (German National Licenses)
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