The Valine Allele of the V89L Polymorphism in the 5-α-Reductase Gene Confers a Reduced Risk for Hypospadias

2005 ◽  
Vol 90 (12) ◽  
pp. 6695-6698 ◽  
Author(s):  
Hanh T. T. Thai ◽  
Mina Kalbasi ◽  
Kristina Lagerstedt ◽  
Louise Frisén ◽  
Ingrid Kockum ◽  
...  
Keyword(s):  
Functional Importance ◽  
Complex Disorders ◽  
Functional Polymorphisms ◽  
Srd5a2 Gene ◽  
Reductase Gene ◽  
Genital Development ◽  
Key Enzyme ◽  
Sporadic Cases ◽  
Valine Allele ◽  
Male Genital

Context: Hypospadias is one of the most common malformations in man, with an incidence of 1:300 in newborn boys. No gene has been identified that causes isolated hypospadias, but the androgenic influence is important during male genital development. Objective: A key enzyme for the androgenic function is steroid 5-α-reductase (SRD5A2). The V89L polymorphism in the SRD5A2 gene has been studied and found to be of functional importance. The leucine version of the enzyme is 30% less efficient than the valine variant. Design, Setting, Patients, and Results: We have genotyped 158 hypospadias cases and 96 unaffected controls for this polymorphism and found a significant negative association for the V89 allele in hypospadias (odds ratio, 0.24; 95% confidence interval, 0.14–0.41 for homozygous individuals). This indicates that a fully functional 5-α-reductase enzyme (homozygous for V89) protects the male urethral development. This association is shown regardless of heredity, ethnicity, and severity of phenotype. We have also sequenced a selected material of 37 sporadic cases of more severe hypospadias for mutations in the androgen receptor AR, SRD5A2, and 17β-hydroxysteroid dehydrogenase HSD17B3 genes and found only two previously described mutations, one in the AR and one in the SRD5A2 gene. Conclusion: This finding is in accordance with the assumption that functional polymorphisms may play an important role in complex disorders such as hypospadias when several genes as well as environmental factors contribute to the etiology.

scholarly journals Functional replacement ofDrosophilaBtk29A with human Btk in male genital development and survival

FEBS Letters ◽  
2005 ◽  
Vol 579 (19) ◽  
pp. 4131-4137 ◽  
Author(s):  
Noriko Hamada ◽  
Carl-Magnus Bäckesjö ◽  
C.I. Edvard Smith ◽  
Daisuke Yamamoto
Keyword(s):  
Genital Development ◽  
Functional Replacement ◽  
Male Genital

scholarly journals A Cell Model for Conditional Profiling of Androgen-Receptor-Interacting Proteins

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
K. A. Mooslehner ◽  
J. D. Davies ◽  
I. A. Hughes
Keyword(s):  
Androgen Receptor ◽  
Protein Interactions ◽  
Cell Model ◽  
Mouse Cell ◽  
Interacting Proteins ◽  
Wild Type ◽  
Genital Development ◽  
A Cell ◽  
The Impact ◽  
Male Genital

Partial androgen insensitivity syndrome (PAIS) is associated with impaired male genital development and can be transmitted through mutations in the androgen receptor (AR). The aim of this study is to develop a cell model suitable for studying the impact AR mutations might have on AR interacting proteins. For this purpose, male genital development relevant mouse cell lines were genetically modified to express a tagged version of wild-type AR, allowing copurification of multiprotein complexes under native conditions followed by mass spectrometry. We report 57 known wild-type AR-interacting proteins identified in cells grown under proliferating and 65 under nonproliferating conditions. Of those, 47 were common to both samples suggesting different AR protein complex components in proliferating and proliferation-inhibited cells from the mouse proximal caput epididymus. These preliminary results now allow future studies to focus on replacing wild-type AR with mutant AR to uncover differences in protein interactions caused by AR mutations involved in PAIS.

In utero effects of maternal phthalate exposure on male genital development

2019 ◽  
Vol 39 (3) ◽  
pp. 209-218 ◽  
Author(s):  
Rebecca J. Wineland ◽  
Michael S. Bloom ◽  
Lori Cruze ◽  
Celeste D. Butts ◽  
Abby G. Wenzel ◽  
...  
Keyword(s):  
In Utero ◽  
Phthalate Exposure ◽  
Genital Development ◽  
Male Genital

scholarly journals Lovastatin inAspergillus terreus: Fermented Rice Straw Extracts Interferes with Methane Production and Gene Expression inMethanobrevibacter smithii

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Mohammad Faseleh Jahromi ◽  
Juan Boo Liang ◽  
Yin Wan Ho ◽  
Rosfarizan Mohamad ◽  
Yong Meng Goh ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Rice Straw ◽  
Methanogenic Archaea ◽  
Feed Additive ◽  
Transmission Electron ◽  
Reductase Gene ◽  
Key Enzyme ◽  
Gene Transcripts ◽  
Coa Reductase

Lovastatin, a natural byproduct of some fungi, is able to inhibit HMG-CoA (3-hydroxy-3methyl glutaryl CoA) reductase. This is a key enzyme involved in isoprenoid synthesis and essential for cell membrane formation in methanogenic Archaea. In this paper, experiments were designed to test the hypothesis that lovastatin secreted byAspergillus terreusin fermented rice straw extracts (FRSE) can inhibit growth and CH4production inMethanobrevibacter smithii(a test methanogen). By HPLC analysis, 75% of the total lovastatin in FRSE was in the active hydroxyacid form, andin vitrostudies confirmed that this had a stronger effect in reducing both growth and CH4production inM. smithiicompared to commercial lovastatin. Transmission electron micrographs revealed distorted morphological divisions of lovastatin- and FRSE-treatedM. smithiicells, supporting its role in blocking normal cell membrane synthesis. Real-time PCR confirmed that both commercial lovastatin and FRSE increased (P<0.01) the expression of HMG-CoA reductase gene (hmg). In addition, expressions of other gene transcripts inM. smithii. with a key involvement in methanogenesis were also affected. Experimental confirmation that CH4production is inhibited by lovastatin inA. terreus-fermented rice straw paves the way for its evaluation as a feed additive for mitigating CH4production in ruminants.

scholarly journals Evidence that luteinising hormone receptor polymorphisms may contribute to male undermasculinisation

2002 ◽  
pp. 103-107 ◽  
Author(s):  
NP Mongan ◽  
IA Hughes ◽  
HN Lim
Keyword(s):  
Hormone Receptor ◽  
Luteinising Hormone ◽  
Pcr Amplification ◽  
Enzyme Analysis ◽  
Control Group ◽  
Restriction Enzyme Analysis ◽  
Control Groups ◽  
Genital Development ◽  
And Control ◽  
Male Genital

BACKGROUND: The luteinising hormone receptor (LHR) is necessary for the stimulation of androgen production and male genital development. It contains three protein polymorphisms: a leucine and glutamine insertion between codons 8 and 9 (LQ+) and two amino acid substitutions (N291S, N312S). OBJECTIVES: To determine whether these LHR polymorphisms are associated with male genital undermasculinisation or the androgen receptor polyglutamine repeat polymorphism (AR(Q)n), which contributes in some cases to the cause of genital undermasculinisation. METHODS: The LHR polymorphisms were assessed by PCR amplification of genomic DNA, followed by restriction enzyme analysis. The frequency of the LHR polymorphisms were compared between an undermasculinised male group (n=75) and a control group (n=55). RESULTS: LQ+ was not independently associated with the undermasculinised group (P=0.09), but it was associated with increased AR(Q)n within the undermasculinised group (P=0.02), particularly for AR(Q)n lengths >or=26 (P=0.002). In the undermasculinised group, homozygosity for N291 (872A/A) was more frequent (P=0.05), whereas homozygosity for N312 (935A/A) was less frequent (P=0.05). The combination of the presence of 872A/A and the absence of 935A/A showed a stronger association with the undermasculinised group than either polymorphism independently (P=0.006). The odds ratio of this genotype compared with any other, between the undermasculinised and control groups was 3.28 (95% confidence interval (CI) 1.33 to 8.08). CONCLUSION: LHR polymorphisms may contribute to genital undermasculinisation.

Expanding DSD Phenotypes Associated with Variants in the DEAH-Box RNA Helicase DHX37

2021 ◽  
pp. 1-9
Author(s):  
Housna Zidoune ◽  
Laetitia Martinerie ◽  
Daisylyn S. Tan ◽  
Masomeh Askari ◽  
Djalila Rezgoune ◽  
...  
Keyword(s):  
Gonadal Dysgenesis ◽  
Ribosome Biogenesis ◽  
Rna Helicase ◽  
Loss Of Function ◽  
Xy Gonadal Dysgenesis ◽  
Testicular Regression ◽  
Genital Development ◽  
Testicular Regression Syndrome ◽  
Complete Gonadal Dysgenesis ◽  
Male Genital

Missense variants in the RNA-helicase DHX37 are associated with either 46,XY gonadal dysgenesis or 46,XY testicular regression syndrome (TRS). DHX37 is required for ribosome biogenesis, and this subgroup of XY DSD is a new human ribosomopathy. In a cohort of 140 individuals with 46,XY DSD, we identified 7 children with either 46,XY complete gonadal dysgenesis or 46,XY TRS carrying rare or novel DHX37 variants. A novel p.R390H variant within the RecA1 domain was identified in a girl with complete gonadal dysgenesis. A paternally inherited p.R487H variant, previously associated with a recessive congenital developmental syndrome, was carried by a boy with a syndromic form of 46,XY DSD. His phenotype may be explained in part by a novel homozygous loss-of-function variant in the <i>NGLY1</i> gene, which causes a congenital disorder of deglycosylation. Remarkably, a homozygous p.T477H variant was identified in a boy with TRS. His fertile father had unilateral testicular regression with typical male genital development. This expands the DSD phenotypes associated with DHX37. Structural analysis of all variants predicted deleterious effects on helicase function. Similar to all other known ribosomopathies, the mechanism of pathogenesis is unknown.

Morphologic differences between abdominal and inguinal testes in stallions

1987 ◽  
Vol 45 ◽  
pp. 820-821
Author(s):  
F. Al-Bagdadi ◽  
D. Hoyt ◽  
P. Karns ◽  
G. Martin ◽  
M. Memon ◽  
...  
Keyword(s):  
Carcinoma Cells ◽  
Genital System ◽  
Diagnosis And Prognosis ◽  
Male Genital System ◽  
Morphological Differences ◽  
Hormone Imbalance ◽  
Made In ◽  
Male Genital

The most frequently occuring abnormality of the male genital system in mammals is the failure of one or both testes to descend into the scrotum. The reasons for abdominal or inguinal retention of testes could be anatomic malformation, faulty development or hormone imbalance.Cryptorchidism has been associated with either greatly reduced or absent spermatogenesis (Kaueakami et al, 1984), and being a source of neoplasia. According to Stick (1980), germinal carcinoma cells have been believed to be the cause of teratomas in equine cryptorchid testicles. Neoplasia has been reported in descended testes of unilateral cryptorchid patients (Martin et al, 1981).No distinction has been made in relating the problem of cryptorchid testes to inguinal or abdominal retention. The purpose of this study is to record the morphological differences between inguinal and abdominal cryptorchid testes as an aid in diagnosis and prognosis.

Membrane microdomains: lessons from microscopy

1995 ◽  
Vol 53 ◽  
pp. 776-777
Author(s):  
J.M. Robinson ◽  
J.M Oliver
Keyword(s):  
Spatial Distribution ◽  
Plasma Membrane ◽  
Epithelial Cells ◽  
Plasma Membranes ◽  
Cell Types ◽  
Imaging Modalities ◽  
Membrane Microdomains ◽  
Membrane Domains ◽  
Lateral Heterogeneity ◽  
Functional Importance

Specialized regions of plasma membranes displaying lateral heterogeneity are the focus of this Symposium. Specialized membrane domains are known for certain cell types such as differentiated epithelial cells where lateral heterogeneity in lipids and proteins exists between the apical and basolateral portions of the plasma membrane. Lateral heterogeneity and the presence of microdomains in membranes that are uniform in appearance have been more difficult to establish. Nonetheless a number of studies have provided evidence for membrane microdomains and indicated a functional importance for these structures.This symposium will focus on the use of various imaging modalities and related approaches to define membrane microdomains in a number of cell types. The importance of existing as well as emerging imaging technologies for use in the elucidation of membrane microdomains will be highlighted. The organization of membrane microdomains in terms of dimensions and spatial distribution is of considerable interest and will be addressed in this Symposium.

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