5α-Reductase, an enzyme regulating glucocorticoid action in the testis of Rhinella arenarum (Amphibia: Anura)
The reduction of A-ring of glucocorticoids to produce 5α-dihydro-derivatives by 5α-reductases has been considered as a pathway of irreversible inactivation. However, 5α-reduced metabolites of corticosterone and testosterone have significant biological activity. In this paper, we investigated whether...
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paper:paper_00166480_v176_n3_p500_Tesone2023-06-08T14:38:19Z 5α-Reductase, an enzyme regulating glucocorticoid action in the testis of Rhinella arenarum (Amphibia: Anura) Regueira, Eleonora Canosa, Luis Fabián Ceballos, Nora Raquel 5α-Reductase Androgens Glucocorticoid-receptor Toad testes 5alpha dihydrocorticosterone corticosterone dexamethasone glucocorticoid glucocorticoid receptor steroid 5alpha reductase testosterone unclassified drug animal tissue article binding affinity biotransformation controlled study cytosol enzyme activity enzyme kinetics enzyme localization enzyme substrate frogs and toads hormone action hormone receptor interaction in vitro study male microsome nonhuman pH priority journal reproduction Rhinella arenarum testis The reduction of A-ring of glucocorticoids to produce 5α-dihydro-derivatives by 5α-reductases has been considered as a pathway of irreversible inactivation. However, 5α-reduced metabolites of corticosterone and testosterone have significant biological activity. In this paper, we investigated whether toad testicular 5α-reductase (5α-Red) is able to transform corticosterone into 5α-dihydrocorticosterone. Furthermore, we studied the role of 5α-reduced metabolite of corticosterone as a glucocorticoid receptor (GR) agonist. The activity of 5α-Red was assayed in subcellular fractions with [3H]corticosterone or [3H]testosterone as substrate. The enzyme localizes 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 5α-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 5α-dihydrocorticosterone (5α-DHB) to the testicular GR show that 5α-DHB 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 5α-DHB were similar, 31.33±2.9nM and 35.24±2.3nM, respectively. In vitro experiments suggest that 5α-DHB 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. © 2012 Elsevier Inc. Fil:Regueira, E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Fabián Canosa, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Ceballos, N.R. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2012 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00166480_v176_n3_p500_Tesone http://hdl.handle.net/20.500.12110/paper_00166480_v176_n3_p500_Tesone |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
5α-Reductase Androgens Glucocorticoid-receptor Toad testes 5alpha dihydrocorticosterone corticosterone dexamethasone glucocorticoid glucocorticoid receptor steroid 5alpha reductase testosterone unclassified drug animal tissue article binding affinity biotransformation controlled study cytosol enzyme activity enzyme kinetics enzyme localization enzyme substrate frogs and toads hormone action hormone receptor interaction in vitro study male microsome nonhuman pH priority journal reproduction Rhinella arenarum testis |
| spellingShingle |
5α-Reductase Androgens Glucocorticoid-receptor Toad testes 5alpha dihydrocorticosterone corticosterone dexamethasone glucocorticoid glucocorticoid receptor steroid 5alpha reductase testosterone unclassified drug animal tissue article binding affinity biotransformation controlled study cytosol enzyme activity enzyme kinetics enzyme localization enzyme substrate frogs and toads hormone action hormone receptor interaction in vitro study male microsome nonhuman pH priority journal reproduction Rhinella arenarum testis Regueira, Eleonora Canosa, Luis Fabián Ceballos, Nora Raquel 5α-Reductase, an enzyme regulating glucocorticoid action in the testis of Rhinella arenarum (Amphibia: Anura) |
| topic_facet |
5α-Reductase Androgens Glucocorticoid-receptor Toad testes 5alpha dihydrocorticosterone corticosterone dexamethasone glucocorticoid glucocorticoid receptor steroid 5alpha reductase testosterone unclassified drug animal tissue article binding affinity biotransformation controlled study cytosol enzyme activity enzyme kinetics enzyme localization enzyme substrate frogs and toads hormone action hormone receptor interaction in vitro study male microsome nonhuman pH priority journal reproduction Rhinella arenarum testis |
| description |
The reduction of A-ring of glucocorticoids to produce 5α-dihydro-derivatives by 5α-reductases has been considered as a pathway of irreversible inactivation. However, 5α-reduced metabolites of corticosterone and testosterone have significant biological activity. In this paper, we investigated whether toad testicular 5α-reductase (5α-Red) is able to transform corticosterone into 5α-dihydrocorticosterone. Furthermore, we studied the role of 5α-reduced metabolite of corticosterone as a glucocorticoid receptor (GR) agonist. The activity of 5α-Red was assayed in subcellular fractions with [3H]corticosterone or [3H]testosterone as substrate. The enzyme localizes 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 5α-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 5α-dihydrocorticosterone (5α-DHB) to the testicular GR show that 5α-DHB 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 5α-DHB were similar, 31.33±2.9nM and 35.24±2.3nM, respectively. In vitro experiments suggest that 5α-DHB 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. © 2012 Elsevier Inc. |
| author |
Regueira, Eleonora Canosa, Luis Fabián Ceballos, Nora Raquel |
| author_facet |
Regueira, Eleonora Canosa, Luis Fabián Ceballos, Nora Raquel |
| author_sort |
Regueira, Eleonora |
| title |
5α-Reductase, an enzyme regulating glucocorticoid action in the testis of Rhinella arenarum (Amphibia: Anura) |
| title_short |
5α-Reductase, an enzyme regulating glucocorticoid action in the testis of Rhinella arenarum (Amphibia: Anura) |
| title_full |
5α-Reductase, an enzyme regulating glucocorticoid action in the testis of Rhinella arenarum (Amphibia: Anura) |
| title_fullStr |
5α-Reductase, an enzyme regulating glucocorticoid action in the testis of Rhinella arenarum (Amphibia: Anura) |
| title_full_unstemmed |
5α-Reductase, an enzyme regulating glucocorticoid action in the testis of Rhinella arenarum (Amphibia: Anura) |
| title_sort |
5α-reductase, an enzyme regulating glucocorticoid action in the testis of rhinella arenarum (amphibia: anura) |
| publishDate |
2012 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00166480_v176_n3_p500_Tesone http://hdl.handle.net/20.500.12110/paper_00166480_v176_n3_p500_Tesone |
| work_keys_str_mv |
AT regueiraeleonora 5areductaseanenzymeregulatingglucocorticoidactioninthetestisofrhinellaarenarumamphibiaanura AT canosaluisfabian 5areductaseanenzymeregulatingglucocorticoidactioninthetestisofrhinellaarenarumamphibiaanura AT ceballosnoraraquel 5areductaseanenzymeregulatingglucocorticoidactioninthetestisofrhinellaarenarumamphibiaanura |
| _version_ |
1768544303562358784 |