5alpha-reductase, an enzyme regulating glucocorticoid action in the testis of Rhinella arenartum (Amphibia, Anura)

Autores
Tesone, Amelia J.; Regueira, Eleonora; Canosa, Luis Fabian; Ceballos, Nora Raquel
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The reduction of A-ring of glucocorticoids to produce 5a-dihydro-derivatives by 5a-reductases has been considered as a pathway of irreversible inactivation. However, 5a-reduced metabolites of corticosterone and testosterone have significant biological activity. In this paper, we investigated whether toad testicular 5a-reductase (5a-Red) is able to transform corticosterone into 5a-dihydrocorticosterone. Furthermore, we studied the role of 5a-reduced metabolite of corticosterone as a glucocorticoid receptor (GR) agonist. The activity of 5a-Red was assayed in subcellular fractions with [3H]corticosterone or [3H]testosterone as substrate. The enzyme localises in microsomes and its optimal pH is between 7 and 8. The activity is not inhibited by finasteride. These results support the conclusion that toad 5a-Red resembles mammalian type 1 isoenzyme. Kinetic studies indicate that neither Km nor Vmax for both corticosterone and testosterone were significantly different among reproductive periods. The Km value for testosterone was significantly higher than that for corticosterone, indicating that the C-21 steroid is the preferred substrate for the enzyme. Studies of the binding capacity of 5a-dihydrocorticosterone (5aDHB) to the testicular GR show that 5aDHB is able to displace the binding of [3H]dexamethasone to testicular cytosol with a similar potency than corticosterone. The inhibition constant (Ki) values for corticosterone and 5aDHB were similar, 31.33 ± 2.9 nM and 35.24 ± 2.3 nM, respectively. In vitro experiments suggest that 5aDHB is an agonist of toad testicular GR, decreasing the activity of the key enzyme for androgen synthesis, the cytochrome P450 17-hydroxylase, C17,20-lyase.
Fil: Tesone, Amelia J.. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental. Laboratorio de Endocrinología Comparada; Argentina
Fil: Regueira, Eleonora. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental. Laboratorio de Endocrinología Comparada; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria; Argentina
Fil: Canosa, Luis Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
Fil: Ceballos, Nora Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental. Laboratorio de Endocrinología Comparada; Argentina
Materia
5Α-REDUCTASE
ANDROGENS
GLUCOCORTICOID-RECEPTOR
TOAD TESTES
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/198539
Acceder
id CONICETDig_22f54ab2e8221bd8cf82def615109d45
oai_identifier_str oai:ri.conicet.gov.ar:11336/198539
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 5alpha-reductase, an enzyme regulating glucocorticoid action in the testis of Rhinella arenartum (Amphibia, Anura)Tesone, Amelia J.Regueira, EleonoraCanosa, Luis FabianCeballos, Nora Raquel5Α-REDUCTASEANDROGENSGLUCOCORTICOID-RECEPTORTOAD TESTEShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The reduction of A-ring of glucocorticoids to produce 5a-dihydro-derivatives by 5a-reductases has been considered as a pathway of irreversible inactivation. However, 5a-reduced metabolites of corticosterone and testosterone have significant biological activity. In this paper, we investigated whether toad testicular 5a-reductase (5a-Red) is able to transform corticosterone into 5a-dihydrocorticosterone. Furthermore, we studied the role of 5a-reduced metabolite of corticosterone as a glucocorticoid receptor (GR) agonist. The activity of 5a-Red was assayed in subcellular fractions with [3H]corticosterone or [3H]testosterone as substrate. The enzyme localises in microsomes and its optimal pH is between 7 and 8. The activity is not inhibited by finasteride. These results support the conclusion that toad 5a-Red resembles mammalian type 1 isoenzyme. Kinetic studies indicate that neither Km nor Vmax for both corticosterone and testosterone were significantly different among reproductive periods. The Km value for testosterone was significantly higher than that for corticosterone, indicating that the C-21 steroid is the preferred substrate for the enzyme. Studies of the binding capacity of 5a-dihydrocorticosterone (5aDHB) to the testicular GR show that 5aDHB is able to displace the binding of [3H]dexamethasone to testicular cytosol with a similar potency than corticosterone. The inhibition constant (Ki) values for corticosterone and 5aDHB were similar, 31.33 ± 2.9 nM and 35.24 ± 2.3 nM, respectively. In vitro experiments suggest that 5aDHB is an agonist of toad testicular GR, decreasing the activity of the key enzyme for androgen synthesis, the cytochrome P450 17-hydroxylase, C17,20-lyase.Fil: Tesone, Amelia J.. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental. Laboratorio de Endocrinología Comparada; ArgentinaFil: Regueira, Eleonora. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental. Laboratorio de Endocrinología Comparada; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria; ArgentinaFil: Canosa, Luis Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Ceballos, Nora Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental. Laboratorio de Endocrinología Comparada; ArgentinaAcademic Press Inc Elsevier Science2012-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/198539Tesone, Amelia J.; Regueira, Eleonora; Canosa, Luis Fabian; Ceballos, Nora Raquel; 5alpha-reductase, an enzyme regulating glucocorticoid action in the testis of Rhinella arenartum (Amphibia, Anura); Academic Press Inc Elsevier Science; General and Comparative Endocrinology; 176; 3; 5-2012; 500-5060016-6480CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0016648012000299?via%3Dihubinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.ygcen.2012.01.004info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:20:52Zoai:ri.conicet.gov.ar:11336/198539instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 15:20:52.362CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv 5alpha-reductase, an enzyme regulating glucocorticoid action in the testis of Rhinella arenartum (Amphibia, Anura)
title 5alpha-reductase, an enzyme regulating glucocorticoid action in the testis of Rhinella arenartum (Amphibia, Anura)
spellingShingle 5alpha-reductase, an enzyme regulating glucocorticoid action in the testis of Rhinella arenartum (Amphibia, Anura)
Tesone, Amelia J.
5Α-REDUCTASE
ANDROGENS
GLUCOCORTICOID-RECEPTOR
TOAD TESTES
title_short 5alpha-reductase, an enzyme regulating glucocorticoid action in the testis of Rhinella arenartum (Amphibia, Anura)
title_full 5alpha-reductase, an enzyme regulating glucocorticoid action in the testis of Rhinella arenartum (Amphibia, Anura)
title_fullStr 5alpha-reductase, an enzyme regulating glucocorticoid action in the testis of Rhinella arenartum (Amphibia, Anura)
title_full_unstemmed 5alpha-reductase, an enzyme regulating glucocorticoid action in the testis of Rhinella arenartum (Amphibia, Anura)
title_sort 5alpha-reductase, an enzyme regulating glucocorticoid action in the testis of Rhinella arenartum (Amphibia, Anura)
dc.creator.none.fl_str_mv Tesone, Amelia J.
Regueira, Eleonora
Canosa, Luis Fabian
Ceballos, Nora Raquel
author Tesone, Amelia J.
author_facet Tesone, Amelia J.
Regueira, Eleonora
Canosa, Luis Fabian
Ceballos, Nora Raquel
author_role author
author2 Regueira, Eleonora
Canosa, Luis Fabian
Ceballos, Nora Raquel
author2_role author
author
author
dc.subject.none.fl_str_mv 5Α-REDUCTASE
ANDROGENS
GLUCOCORTICOID-RECEPTOR
TOAD TESTES
topic 5Α-REDUCTASE
ANDROGENS
GLUCOCORTICOID-RECEPTOR
TOAD TESTES
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The reduction of A-ring of glucocorticoids to produce 5a-dihydro-derivatives by 5a-reductases has been considered as a pathway of irreversible inactivation. However, 5a-reduced metabolites of corticosterone and testosterone have significant biological activity. In this paper, we investigated whether toad testicular 5a-reductase (5a-Red) is able to transform corticosterone into 5a-dihydrocorticosterone. Furthermore, we studied the role of 5a-reduced metabolite of corticosterone as a glucocorticoid receptor (GR) agonist. The activity of 5a-Red was assayed in subcellular fractions with [3H]corticosterone or [3H]testosterone as substrate. The enzyme localises in microsomes and its optimal pH is between 7 and 8. The activity is not inhibited by finasteride. These results support the conclusion that toad 5a-Red resembles mammalian type 1 isoenzyme. Kinetic studies indicate that neither Km nor Vmax for both corticosterone and testosterone were significantly different among reproductive periods. The Km value for testosterone was significantly higher than that for corticosterone, indicating that the C-21 steroid is the preferred substrate for the enzyme. Studies of the binding capacity of 5a-dihydrocorticosterone (5aDHB) to the testicular GR show that 5aDHB is able to displace the binding of [3H]dexamethasone to testicular cytosol with a similar potency than corticosterone. The inhibition constant (Ki) values for corticosterone and 5aDHB were similar, 31.33 ± 2.9 nM and 35.24 ± 2.3 nM, respectively. In vitro experiments suggest that 5aDHB is an agonist of toad testicular GR, decreasing the activity of the key enzyme for androgen synthesis, the cytochrome P450 17-hydroxylase, C17,20-lyase.
Fil: Tesone, Amelia J.. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental. Laboratorio de Endocrinología Comparada; Argentina
Fil: Regueira, Eleonora. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental. Laboratorio de Endocrinología Comparada; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria; Argentina
Fil: Canosa, Luis Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
Fil: Ceballos, Nora Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental. Laboratorio de Endocrinología Comparada; Argentina
description The reduction of A-ring of glucocorticoids to produce 5a-dihydro-derivatives by 5a-reductases has been considered as a pathway of irreversible inactivation. However, 5a-reduced metabolites of corticosterone and testosterone have significant biological activity. In this paper, we investigated whether toad testicular 5a-reductase (5a-Red) is able to transform corticosterone into 5a-dihydrocorticosterone. Furthermore, we studied the role of 5a-reduced metabolite of corticosterone as a glucocorticoid receptor (GR) agonist. The activity of 5a-Red was assayed in subcellular fractions with [3H]corticosterone or [3H]testosterone as substrate. The enzyme localises in microsomes and its optimal pH is between 7 and 8. The activity is not inhibited by finasteride. These results support the conclusion that toad 5a-Red resembles mammalian type 1 isoenzyme. Kinetic studies indicate that neither Km nor Vmax for both corticosterone and testosterone were significantly different among reproductive periods. The Km value for testosterone was significantly higher than that for corticosterone, indicating that the C-21 steroid is the preferred substrate for the enzyme. Studies of the binding capacity of 5a-dihydrocorticosterone (5aDHB) to the testicular GR show that 5aDHB is able to displace the binding of [3H]dexamethasone to testicular cytosol with a similar potency than corticosterone. The inhibition constant (Ki) values for corticosterone and 5aDHB were similar, 31.33 ± 2.9 nM and 35.24 ± 2.3 nM, respectively. In vitro experiments suggest that 5aDHB is an agonist of toad testicular GR, decreasing the activity of the key enzyme for androgen synthesis, the cytochrome P450 17-hydroxylase, C17,20-lyase.
publishDate 2012
dc.date.none.fl_str_mv 2012-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/198539
Tesone, Amelia J.; Regueira, Eleonora; Canosa, Luis Fabian; Ceballos, Nora Raquel; 5alpha-reductase, an enzyme regulating glucocorticoid action in the testis of Rhinella arenartum (Amphibia, Anura); Academic Press Inc Elsevier Science; General and Comparative Endocrinology; 176; 3; 5-2012; 500-506
0016-6480
CONICET Digital
CONICET
url http://hdl.handle.net/11336/198539
identifier_str_mv Tesone, Amelia J.; Regueira, Eleonora; Canosa, Luis Fabian; Ceballos, Nora Raquel; 5alpha-reductase, an enzyme regulating glucocorticoid action in the testis of Rhinella arenartum (Amphibia, Anura); Academic Press Inc Elsevier Science; General and Comparative Endocrinology; 176; 3; 5-2012; 500-506
0016-6480
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0016648012000299?via%3Dihub
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ygcen.2012.01.004
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Academic Press Inc Elsevier Science
publisher.none.fl_str_mv Academic Press Inc Elsevier Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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