Testosterone inhibits human wild-type and chimeric aldosterone synthase activity in vitro Article Swipe
Andrea Vecchiola
,
Cristóbal Fuentes
,
Cristián A. Carvajal
,
Carmen Campino
,
Fidel Allende
,
Alejandra Tapia-Castillo
,
Carlos F. Lagos
,
Carlos Fardella
·
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-51648/v1
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-51648/v1
BackgroundFamilial hyperaldosteronism type I is caused by the generation of a chimeric aldosterone synthase enzyme (ASCE) which is regulated by ACTH instead of angiotensin II. We have reported that in vitro, the wild-type (ASWT) and chimeric aldosterone synthase (ASCE) enzymes are inhibited by progesterone and estradiol did not affect.AimTo explore the direct action of testosterone on ASWT and ASCE enzymes.MethodsHEK-293 cells were transiently transfected with vectors containing the full ASWT or ASCE cDNAs. The effect of testosterone on AS enzyme activities were evaluated incubating HEK-cells transfected with enzymes vectors and adding deoxycorticosterone (DOC) alone or DOC plus increasing doses of testosterone. Aldosterone production was measured by HPLC-MS/MS. Docking of testosterone within the active sites of both enzymes was performed.ResultsIn this system, testosterone inhibited ASWT (90% inhibition at five µM, IC50=1.690 µM) with higher efficacy and potency than ASCE (80% inhibition at five µM, IC50=3.176 µM). Molecular modelling studies showed different orientation of testosterone in ASWT and ASCE crystal structures.ConclusionsThe inhibitory effect of testosterone on ASWT or ASCE enzymes is a novel non-genomic testosterone action, suggesting that further clinical studies are needed to assess the role of testosterone in the screening and diagnosis of primary aldosteronism.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.21203/rs.3.rs-51648/v1
- https://www.researchsquare.com/article/rs-51648/v1.pdf?c=1602389333000
- OA Status
- gold
- References
- 14
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4251120215
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4251120215Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.21203/rs.3.rs-51648/v1Digital Object Identifier
- Title
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Testosterone inhibits human wild-type and chimeric aldosterone synthase activity in vitroWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2020Year of publication
- Publication date
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2020-10-07Full publication date if available
- Authors
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Andrea Vecchiola, Cristóbal Fuentes, Cristián A. Carvajal, Carmen Campino, Fidel Allende, Alejandra Tapia-Castillo, Carlos F. Lagos, Carlos FardellaList of authors in order
- Landing page
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https://doi.org/10.21203/rs.3.rs-51648/v1Publisher landing page
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https://www.researchsquare.com/article/rs-51648/v1.pdf?c=1602389333000Direct link to full text PDF
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://www.researchsquare.com/article/rs-51648/v1.pdf?c=1602389333000Direct OA link when available
- Concepts
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Aldosterone synthase, In vitro, Aldosterone, Testosterone (patch), Endocrinology, Internal medicine, ATP synthase, Biology, Chemistry, Enzyme, Medicine, Biochemistry, Renin–angiotensin system, Blood pressureTop concepts (fields/topics) attached by OpenAlex
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0Total citation count in OpenAlex
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14Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| primary_location.raw_source_name | |
| primary_location.landing_page_url | https://doi.org/10.21203/rs.3.rs-51648/v1 |
| publication_date | 2020-10-07 |
| publication_year | 2020 |
| referenced_works | https://openalex.org/W6684985528, https://openalex.org/W2290633895, https://openalex.org/W6843945467, https://openalex.org/W2160612644, https://openalex.org/W4290171060, https://openalex.org/W1985858914, https://openalex.org/W2126690200, https://openalex.org/W2332210636, https://openalex.org/W1982572530, https://openalex.org/W4406652919, https://openalex.org/W2041781505, https://openalex.org/W2804783428, https://openalex.org/W4231729539, https://openalex.org/W2169857190 |
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