Characterization of the guinea pig 3β-hydroxysteroid dehydrogenase/Δ5–Δ4-isomerase expressed in the adrenal gland and gonads

Durocher, Francine; Sánchez, Rocío; Ricketts, Marie‐Louise; Labrie, Yvan; Laudet, Vincent; Simard, Jacques

doi:10.1016/j.jsbmb.2005.05.011

Cited by 4 publications

(3 citation statements)

References 51 publications

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“…Esta isoenzima ha sido caracterizada en humanos y en otras especies de vertebrados [16][17][18] y se le han documentado sitios catalíticos bifuncionales por medio de diferentes conformaciones para cada actividad [5]. En humanos, el ADN complementario de la enzima 3β-hidroxiesteroide deshidrogenasa tipo 1 fue aislado y caracterizado por Luu-The y colaboradores, en 1988, en la placenta humana [19]; posteriormente fue identificado en diferentes organelas por Thomas y colaboradores [20].…”

Section: Expresión Humana Del Gen De La 3β-hidroxiesteroide Deshidrogenasaunclassified

Deficiencia de 3β-hidroxiesteroide deshidrogenasa: una causa rara de hiperplasia adrenal congénita

et al. 2016

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La hiperplasia adrenal congénita corresponde a un grupo de enfermedades heredadas con defectos enzimáticos que pueden comprometer la biosíntesis del cortisol. La deficiencia de la enzima 3β-hidroxiesteroide deshidrogenasa tipo 2 es una causa rara de este defecto en la que el desarrollo genital masculino se encuentra alterado y presenta una virilización leve en las mujeres afectadas. En humanos se han descrito dos isoenzimas, la tipo I y la tipo II, codificadas por los genes HSD3B1 y HSD3B2, respectivamente, con una distribución tisular específica. Los programas de tamización de la hiperplasia adrenal congénita reportan elevación paradójica de la 17-hidroxiprogesterona secundaria al efecto periférico de la 3β-hidroxiesteroide deshidrogenasa tipo 1, isoenzima de la 3β-hidroxiesteroide deshidrogenasa tipo 2, que tiene una constante de Michaelis menor con el sustrato. A pesar de la baja prevalencia el estudio de este defecto ha tenido importantes avances en cuanto a la información molecular y el diagnóstico hormonal, datos que han sido respaldados por la identificación de la alteración genética y han disminuido la posibilidad del sobrediagnóstico; evento que se estaba presentado frecuentemente con los puntos de cortes establecidos inicialmente para el diagnóstico de la enfermedad, sobre todo en sus formas leves.

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Section: Expresión Humana Del Gen De La 3β-hidroxiesteroide Deshidrogenasaunclassified

Deficiencia de 3β-hidroxiesteroide deshidrogenasa: una causa rara de hiperplasia adrenal congénita

et al. 2016

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“…1,21 Interorganelle and intercellular transports are not included in the model since these processes are assumed to be not rate-limiting and experimental data for these transport rates are unavailable. In addition, since all of the reactions are predominantly irreversible, 13 we set the rates for the reverse reactions to zero. For each reaction, we assume the substrate concentration is much less than the Michaelis constant (substrate concentration that results in a half-maximal reaction rate).…”

Section: Metabolic Reactionsmentioning

confidence: 99%

Mechanistic Computational Model of Ovarian Steroidogenesis to Predict Biochemical Responses to Endocrine Active Compounds

et al. 2007

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Abstract-Sex steroids, which have an important role in a wide range of physiological and pathological processes, are synthesized primarily in the gonads and adrenal glands through a series of enzyme-mediated reactions. The activity of steroidogenic enzymes can be altered by a variety of endocrine active compounds (EAC), some of which are therapeutics and others that are environmental contaminants. A steady-state computational model of the intraovarian metabolic network was developed to predict the synthesis and secretion of testosterone (T) and estradiol (E2), and their responses to EAC. Model predictions were compared to data from an in vitro steroidogenesis assay with ovary explants from a small fish model, the fathead minnow. Model parameters were estimated using an iterative optimization algorithm. Model-predicted concentrations of T and E2 closely correspond to the time-course data from baseline (control) experiments, and dose-response data from experiments with the EAC, fadrozole (FAD). A sensitivity analysis of the model parameters identified specific transport and metabolic processes that most influence the concentrations of T and E2, which included uptake of cholesterol into the ovary, secretion of androstenedione (AD) from the ovary, and conversions of AD to T, and AD to estrone (E1). The sensitivity analysis also indicated the E1 pathway as the preferred pathway for E2 synthesis, as compared to the T pathway. Our study demonstrates the feasibility of using the steroidogenesis model to predict T and E2 concentrations, in vitro, while reducing model complexity with a steady-state assumption. This capability could be useful for pharmaceutical development and environmental health assessments with EAC.

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“…In gonads, steroid-producing cells contain the steroid 17α-monooxygenase (Cyp17a1) that enables pregnenolone to be converted to dehydroepiandrosterone (DHEA) [ 1 ] . As soon as androstenedione is generated from DHEA by the 3β-Hsd enzyme [ 2 ] , it is converted to testosterone by 17β-hydroxysteroid dehydrogenase (Hsd17b1) [ 1 ] . Endogenous estrogens (estrone and estradiol) are generated from C19 androgen (testosterone and androstenedione) by Cyp19a1, an aromatase enzyme [ 3 ] .…”

Section: Introductionmentioning

confidence: 99%

Hydroxylation and sulfation of sex steroid hormones in inflammatory liver

Lee

Kim

et al. 2017

J Biomed Res

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Sex steroids, also known as gonadal steroids, are oxidized with hydroxylation by cytochrome P450, glucuronidation by UDP-glucuronosyltransferase, sulfation by sulfotransferase, andO-methylation by catechol O-methyltransferase. Thus, it is important to determine the process by which inflammation influences metabolism of gonadal hormones. Therefore, we investigated the mechanism of metabolic enzymes against high physiologic inflammatory responsein vivo to study their biochemical properties in liver diseases. In this study, C57BL/6N mice were induced with hepatic inflammation by diethylnitrosamine (DEN) exposure. We observed upregulation of Cyp19a1, Hsd17b1, Cyp1a1, Sult1e1 in the DEN-treated livers compared to the control-treated livers using real time PCR. Moreover, the increased Cyp19a1 and Hsd17b1 levels support the possibility that estrogen biosynthesis from androgens are accumulated during inflammatory liver diseases. Furthermore, the increased levels of Cyp1a1 and Cyp1b1 in the hydroxylation of estrogen facilitated the conversion of estrogen to 2- or 4-hydroxyestrogen, respectively. In addition, the substantial increase in the Sult1e1 enzyme levels could lead to sulfate conjugation of hydroxyestrogen. The present information supports the concept that inflammatory response can sequester sulfate conjugates from the endogenous steroid hormones and may suppress binding of sex steroid hormones to their receptors in the whole body.

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Characterization of the guinea pig 3β-hydroxysteroid dehydrogenase/Δ5–Δ4-isomerase expressed in the adrenal gland and gonads

Cited by 4 publications

References 51 publications

Deficiencia de 3β-hidroxiesteroide deshidrogenasa: una causa rara de hiperplasia adrenal congénita

Deficiencia de 3β-hidroxiesteroide deshidrogenasa: una causa rara de hiperplasia adrenal congénita

Mechanistic Computational Model of Ovarian Steroidogenesis to Predict Biochemical Responses to Endocrine Active Compounds

Hydroxylation and sulfation of sex steroid hormones in inflammatory liver

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