For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
20
views
18
references
 Top references
cited by
69
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      283
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: not found

      Male pseudohermaphroditism caused by mutations of testicular 17 beta-hydroxysteroid dehydrogenase 3.

      Author(s):
      Publication date:
      Journal: Nature genetics
      Keywords: 17-Hydroxysteroid Dehydrogenases, deficiency, genetics, Adolescent, Amino Acid Sequence, Androstenedione, metabolism, Base Sequence, Chromosomes, Human, Pair 9, Cloning, Molecular, DNA, Complementary, Disorders of Sex Development, embryology, Humans, Isoenzymes, Male, Molecular Sequence Data, Mutagenesis, Site-Directed, Organ Specificity, Phenotype, Point Mutation, Sequence Alignment, Sequence Homology, Amino Acid, Testis, enzymology, Testosterone, biosynthesis

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Defects in the conversion of androstenedione to testosterone in the fetal testes by the enzyme 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) give rise to genetic males with female external genitalia. We have used expression cloning to isolate cDNAs encoding a microsomal 17 beta-HSD type 3 isozyme that shares 23% sequence identity with other 17 beta-HSD enzymes, uses NADPh as a cofactor, and is expressed predominantly in the testes. The 17 beta HSD3 gene on chromosome 9q22 contains 11 exons. Four substitution and two splice junction mutations were identified in the 17 beta HSD3 genes of five unrelated male pseudohermaphrodites. The substitution mutations severely compromised the activity of the 17 beta-HSD type 3 isozyme.

          Related collections

          Most cited references18

          • Record: found
          • Abstract: found
          • Article: not found

          Tissue distribution and ontogeny of steroid 5 alpha-reductase isozyme expression.

          Charles Thigpen, Elizabeth J. McConnell, Stuart D. Russell … (1993)
          The synthesis of dihydrotestosterone is catalyzed by steroid 5 alpha-reductase isozymes, designated types 1 and 2. Mutation of type 2 results in male pseudohermaphroditism, in which the external genitalia are phenotypically female at birth. Two striking and unexplained features of this disorder are that external genitalia of affected males undergo virilization during puberty and that these individuals have less temporal hair regression. The tissue-specific and developmental expression patterns of the 5 alpha-reductase isozymes were investigated by immunoblotting. The type 1 isozyme is not detectable in the fetus, is transiently expressed in newborn skin and scalp, and permanently expressed in skin from the time of puberty. There was no qualitative difference in 5 alpha-reductase type 1 expression between adult balding vs. nonbalding scalp. The type 2 isozyme is transiently expressed in skin and scalp of newborns. Type 2 is the predominant isozyme detectable in fetal genital skin, male accessory sex glands, and in the prostate, including benign prostatic hyperplasia and prostate adenocarcinoma tissues. Both isozymes are expressed in the liver, but only after birth. These results are consistent with 5 alpha-reductase type 1 being responsible for virilization in type 2-deficient subjects during puberty, and suggest that the type 2 isozyme may be an initiating factor in development of male pattern baldness.
          Article 0 comments Cited 99 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Deletion of steroid 5 alpha-reductase 2 gene in male pseudohermaphroditism.

            Helen Berman, Håkan Andersson, Stuart D. Russell … (1991)
            The conversion of testosterone into dihydrotestosterone by steroid 5 alpha-reductase is a key reaction in androgen action, and is essential both for the formation of the male phenotype during embryogenesis and for androgen-mediated growth of tissues such as the prostate. Single gene defects that impair this conversion lead to pseudohermaphroditism in which 46X,Y males have male internal urogenital tracts, but female external genitalia. We have described the isolation of a human 5 alpha-reductase complementary DNA from prostate. Subsequent cloning and genetic studies showed that this gene (designated 5 alpha-reductase 1) was normal in patients with 5 alpha-reductase deficiency. We report here the isolation of a second 5 alpha-reductase cDNA by expression cloning and the polymerase chain reaction. The biochemical and pharmacological properties of this cDNA-encoded enzyme (designated 5 alpha-reductase 2) are consistent with it being the major isozyme in genital tissue. A deletion in this gene is present in two related individuals with male pseudohermaphroditism caused by 5 alpha-reductase deficiency. These results verify the existence of at least two 5 alpha-reductases in man and provide insight into a fundamental hormone-mediated event in male sexual differentiation.
            Article 0 comments Cited 77 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Molecular genetics of steroid 5 alpha-reductase 2 deficiency.

              Berenice Mendonca, Ian Davis, Machelle D. Wilson … (1992)
              Two isozymes of steroid 5 alpha-reductase encoded by separate loci catalyze the conversion of testosterone to dihydrotestosterone. Inherited defects in the type 2 isozyme lead to male pseudohermaphroditism in which affected males have a normal internal urogenital tract but external genitalia resembling those of a female. The 5 alpha-reductase type 2 gene (gene symbol SRD5A2) was cloned and shown to contain five exons and four introns. The gene was localized to chromosome 2 band p23 by somatic cell hybrid mapping and chromosomal in situ hybridization. Molecular analysis of the SRD5A2 gene resulted in the identification of 18 mutations in 11 homozygotes, 6 compound heterozygotes, and 4 inferred compound heterozygotes from 23 families with 5 alpha-reductase deficiency. 6 apparent recurrent mutations were detected in 19 different ethnic backgrounds. In two patients, the catalytic efficiency of the mutant enzymes correlated with the severity of the disease. The high proportion of compound heterozygotes suggests that the carrier frequency of mutations in the 5 alpha-reductase type 2 gene may be higher than previously thought.
              Article 0 comments Cited 49 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                PubMed ID:: 8075637
                DOI:: 10.1038/ng0594-34

                ScienceOpen disciplines: Chemistry
                Keywords: 17-Hydroxysteroid Dehydrogenases,deficiency,genetics,Adolescent,Amino Acid Sequence,Androstenedione,metabolism,Base Sequence,Chromosomes, Human, Pair 9,Cloning, Molecular,DNA, Complementary,Disorders of Sex Development,embryology,Humans,Isoenzymes,Male,Molecular Sequence Data,Mutagenesis, Site-Directed,Organ Specificity,Phenotype,Point Mutation,Sequence Alignment,Sequence Homology, Amino Acid,Testis,enzymology,Testosterone,biosynthesis
                Data availability:
                ScienceOpen disciplines: Chemistry
                Keywords: 17-Hydroxysteroid Dehydrogenases, deficiency, genetics, Adolescent, Amino Acid Sequence, Androstenedione, metabolism, Base Sequence, Chromosomes, Human, Pair 9, Cloning, Molecular, DNA, Complementary, Disorders of Sex Development, embryology, Humans, Isoenzymes, Male, Molecular Sequence Data, Mutagenesis, Site-Directed, Organ Specificity, Phenotype, Point Mutation, Sequence Alignment, Sequence Homology, Amino Acid, Testis, enzymology, Testosterone, biosynthesis

                Comments

                Comment on this article

                scite_

                Similar content283

                See all similar

                Cited by68

                See all cited by

                Most referenced authors134

                See all reference authors