Response to treatment in patients with partial androgen insensitivity due to mutations in the DNA-binding domain of the androgen receptor
(2000) In Hormone Research 53(2). p.83-88- Abstract
The androgen insensitivity syndrome is a disorder caused by deficient function of the androgen receptor, characterized by varying degrees of undermasculinization in karyotypic males. We have identified four mutations in the androgen receptor gene, in the region encoding the DNA-binding domain of the protein. Two mutations, R607X and R615G, were found in patients with complete insensitivity to androgens, whereas the other two, S578T and A596T, were found in patients with partial insensitivity. The functional consequences of the three missense mutations were assayed in vitro after transient expression of the receptors in COS cells. All mutants showed normal androgen binding but abnormal abilities to stimulate transcription of an... (More)
The androgen insensitivity syndrome is a disorder caused by deficient function of the androgen receptor, characterized by varying degrees of undermasculinization in karyotypic males. We have identified four mutations in the androgen receptor gene, in the region encoding the DNA-binding domain of the protein. Two mutations, R607X and R615G, were found in patients with complete insensitivity to androgens, whereas the other two, S578T and A596T, were found in patients with partial insensitivity. The functional consequences of the three missense mutations were assayed in vitro after transient expression of the receptors in COS cells. All mutants showed normal androgen binding but abnormal abilities to stimulate transcription of an androgen-responsive reporter gene. R615G abolished transactivation whereas S578T and A596T were partially malfunctional. The function of A596T, but not of S578T, was normalized at high androgen concentrations in vitro, reflecting the in vivo situation. Thus, patients with specific mutations in the DNA- binding domain of the androgen receptor may benefit from androgen treatment. Copyright (C) 2000 S. Karger AG, Basel.
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- author
- Giwercman, Yvonne Lundberg LU ; Nikoshkov, Andrej ; Lindsten, Kristina ; Byström, Birgitta ; Pousette, Ake ; Knudtzon, Jørgen ; Alm, Jan and Wedell, Anna
- publishing date
- 2000-09-23
- type
- Contribution to journal
- publication status
- published
- keywords
- Androgen insensitivity, Androgen receptor, Mutations
- in
- Hormone Research
- volume
- 53
- issue
- 2
- pages
- 83 - 88
- publisher
- Karger
- external identifiers
-
- pmid:10971094
- scopus:0033813598
- ISSN
- 0301-0163
- language
- English
- LU publication?
- no
- id
- 8629d010-e87d-4a9b-a6cf-7807c2d454b0
- date added to LUP
- 2019-05-23 09:47:55
- date last changed
- 2024-05-01 09:30:42
@article{8629d010-e87d-4a9b-a6cf-7807c2d454b0,
abstract = {{<p>The androgen insensitivity syndrome is a disorder caused by deficient function of the androgen receptor, characterized by varying degrees of undermasculinization in karyotypic males. We have identified four mutations in the androgen receptor gene, in the region encoding the DNA-binding domain of the protein. Two mutations, R607X and R615G, were found in patients with complete insensitivity to androgens, whereas the other two, S578T and A596T, were found in patients with partial insensitivity. The functional consequences of the three missense mutations were assayed in vitro after transient expression of the receptors in COS cells. All mutants showed normal androgen binding but abnormal abilities to stimulate transcription of an androgen-responsive reporter gene. R615G abolished transactivation whereas S578T and A596T were partially malfunctional. The function of A596T, but not of S578T, was normalized at high androgen concentrations in vitro, reflecting the in vivo situation. Thus, patients with specific mutations in the DNA- binding domain of the androgen receptor may benefit from androgen treatment. Copyright (C) 2000 S. Karger AG, Basel.</p>}},
author = {{Giwercman, Yvonne Lundberg and Nikoshkov, Andrej and Lindsten, Kristina and Byström, Birgitta and Pousette, Ake and Knudtzon, Jørgen and Alm, Jan and Wedell, Anna}},
issn = {{0301-0163}},
keywords = {{Androgen insensitivity; Androgen receptor; Mutations}},
language = {{eng}},
month = {{09}},
number = {{2}},
pages = {{83--88}},
publisher = {{Karger}},
series = {{Hormone Research}},
title = {{Response to treatment in patients with partial androgen insensitivity due to mutations in the DNA-binding domain of the androgen receptor}},
volume = {{53}},
year = {{2000}},
}