Tags

Type your tag names separated by a space and hit enter

Detailed functional studies on androgen receptor mild mutations demonstrate their association with male infertility.
Clin Endocrinol (Oxf). 2008 Apr; 68(4):580-8.CE

Abstract

CONTEXT

Mutations in the androgen receptor (AR) gene can cause the androgen insensitivity syndrome (AIS). For complete and severe partial AIS, well-characterized in vitro functional assays can be used for genotype-phenotype correlation; however, for mild forms of AIS, as associated with male infertility, experimental evidence is scarce or lacking. In particular, optimal in vitro functional tests informative about the genotype-phenotype relation have not been described.

OBJECTIVE

The objective of this study was to investigate the association among genotype and phenotype for AR mutations found in infertile males by conventional functional assays and additional in-depth studies performed with several gene reporters.

DESIGN

To this aim, we selected four AR missense mutations associated with isolated male infertility (L547F and two novel mutations A474V and S650G) or partial AIS (Y571H). After introduction of the specific mutations in AR expression plasmid, we performed classical in vitro studies (Western immunoblotting, electrophoretic mobility shift assay, hormone-response curves) and transactivation assays with different reporter constructs (MMTV, Sc-ARU-TK, TAT-GRE- 2X, Slp-ARU-TK and PEM).

RESULTS AND CONCLUSIONS

Our results showed that standard functional tests provide sufficient information only for severe AR mutations, whereas for AR mutations found in mild AIS patients with male infertility, only an extensive analysis with different in vitro systems, and in particular with PEM promoter, can give information on the functionality of the AR and therefore on the pathogenicity of the mutations and on genotype-phenotype correlation.

Authors+Show Affiliations

Department of Histology, Microbiology and Medical Biotechnology, University of Padova, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17970778

Citation

Zuccarello, D, et al. "Detailed Functional Studies On Androgen Receptor Mild Mutations Demonstrate Their Association With Male Infertility." Clinical Endocrinology, vol. 68, no. 4, 2008, pp. 580-8.
Zuccarello D, Ferlin A, Vinanzi C, et al. Detailed functional studies on androgen receptor mild mutations demonstrate their association with male infertility. Clin Endocrinol (Oxf). 2008;68(4):580-8.
Zuccarello, D., Ferlin, A., Vinanzi, C., Prana, E., Garolla, A., Callewaert, L., Claessens, F., Brinkmann, A. O., & Foresta, C. (2008). Detailed functional studies on androgen receptor mild mutations demonstrate their association with male infertility. Clinical Endocrinology, 68(4), 580-8.
Zuccarello D, et al. Detailed Functional Studies On Androgen Receptor Mild Mutations Demonstrate Their Association With Male Infertility. Clin Endocrinol (Oxf). 2008;68(4):580-8. PubMed PMID: 17970778.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Detailed functional studies on androgen receptor mild mutations demonstrate their association with male infertility. AU - Zuccarello,D, AU - Ferlin,A, AU - Vinanzi,C, AU - Prana,E, AU - Garolla,A, AU - Callewaert,L, AU - Claessens,F, AU - Brinkmann,A O, AU - Foresta,C, Y1 - 2007/10/29/ PY - 2007/11/1/pubmed PY - 2009/9/1/medline PY - 2007/11/1/entrez SP - 580 EP - 8 JF - Clinical endocrinology JO - Clin Endocrinol (Oxf) VL - 68 IS - 4 N2 - CONTEXT: Mutations in the androgen receptor (AR) gene can cause the androgen insensitivity syndrome (AIS). For complete and severe partial AIS, well-characterized in vitro functional assays can be used for genotype-phenotype correlation; however, for mild forms of AIS, as associated with male infertility, experimental evidence is scarce or lacking. In particular, optimal in vitro functional tests informative about the genotype-phenotype relation have not been described. OBJECTIVE: The objective of this study was to investigate the association among genotype and phenotype for AR mutations found in infertile males by conventional functional assays and additional in-depth studies performed with several gene reporters. DESIGN: To this aim, we selected four AR missense mutations associated with isolated male infertility (L547F and two novel mutations A474V and S650G) or partial AIS (Y571H). After introduction of the specific mutations in AR expression plasmid, we performed classical in vitro studies (Western immunoblotting, electrophoretic mobility shift assay, hormone-response curves) and transactivation assays with different reporter constructs (MMTV, Sc-ARU-TK, TAT-GRE- 2X, Slp-ARU-TK and PEM). RESULTS AND CONCLUSIONS: Our results showed that standard functional tests provide sufficient information only for severe AR mutations, whereas for AR mutations found in mild AIS patients with male infertility, only an extensive analysis with different in vitro systems, and in particular with PEM promoter, can give information on the functionality of the AR and therefore on the pathogenicity of the mutations and on genotype-phenotype correlation. SN - 1365-2265 UR - https://www.unboundmedicine.com/medline/citation/17970778/Detailed_functional_studies_on_androgen_receptor_mild_mutations_demonstrate_their_association_with_male_infertility_ L2 - https://doi.org/10.1111/j.1365-2265.2007.03069.x DB - PRIME DP - Unbound Medicine ER -