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Authors
Abstract(s)
A enzima 5α‐reductase (5α‐R) metaboliza a testosterona (T) a um androgénio
activo, a 5α‐dihidrotestosterona (DHT), em tecidos periféricos incluindo diversas
regiões do cérebro. Recentemente o nosso grupo de investigação demonstrou a
presença do mRNA da 5α‐reductase no plexo coróide (CP) de rato. O plexo coróide é
responsável pela produção do fluido cerebroespinhal e também apresenta
capacidades neuroprotectoras. Durante o processo de envelhecimento, o CP apresenta
um declínio em todos os aspectos da sua função, o que pode aumentar o risco de
doenças neurodegenerativas. A presença da 5α‐R no CP sugere que a produção de
androgénios pode ocorrer localmente neste órgão. Contudo, não há estudos que
caracterizem a actividade da 5α‐R ou que identifiquem os factores que regulam a sua
expressão no CP. Com o objectivo de começar a clarificar estas questões, foram
delineados os seguintes objectivos: i) confirmar a presença da proteína 5α‐R no CP; ii)
estudar a expressão da 5α‐R durante o envelhecimento; iii) demonstrar a bioactividade
da 5α‐R no CP. As análises por Imunohistoquímica e Western Blot confirmaram a
presença da proteína 5α‐R no CP de rato. Foram removidos CPs de ratos macho e
fêmea com diferentes idades (3, 6, 9 e 12 meses), extraiu‐se o RNA total usado
posteriormente para síntese de cDNA. Por RT‐PCR analisou‐se a expressão da 5α‐R no
CP de ratos durante o envelhecimento. Os resultados obtidos demonstraram que a
expressão da 5α‐R é regulada positivamente aos 9 e 12 meses de idade em ratos
macho (P<0,005), o que pode estar associado com a redução de produção de
testosterona observada em animais destas idades1. A fim de obter informação sobre a
actividade da 5α‐R, foram realizadas culturas ex vivo de CP com [3H]‐T, monitorizando
a sua conversão em [3H]‐DHT por cromatografia em camada fina. O tecido de CP não
apresenta uma conversão significativa de [3H]‐T a [3H]‐DHT, no entanto os resultados
não foram conclusivos. Estudos futuros deverão ser realizados de modo a confirmar a
actividade da 5α‐R no CP.
1. Zirkin et. al (1997). Leydig cell steroidogenesis in aging rats. Exp. Gerontol. 32 (4‐
5):529‐37.
The enzyme 5α‐reductase (5α‐R) metabolizes testosterone (T) to an active androgen, 5α‐dihydrotestosterone (DHT), in pheripheral tissues, including several brain regions. Recently our research group demonstrated the presence of 5α‐R mRNA in rat choroid plexus (CP). CP is responsible for the production of cerebrospinal fluid and also displays neuroprotective capabilities. During the aging process the CP shows a decline in all aspects of its function, which may increase the risk for development of neurodegenerative diseases. The presence of 5α‐R in CP suggests that androgens production may occur locally in this organ. However, there are no studies directed to the characterization of 5α‐R activity or to the identification of factors that regulate its expression in CP. In order to start clarifying these issues the following objectives were delineated: i) to confirm the presence of 5α‐R protein in rat CP; ii) to study the expression of 5α‐R during aging; iii) to demonstrate the bioactivity of 5α‐R in CP. Immunohistochemistry and Western blot analysis confirmed the presence of 5α‐R protein in rat CP. CPs were removed from male and female rats at different postnatal ages (3, 6, 9 and 12 month‐old), total RNA was extracted and used for cDNA synthesis. Real‐time PCR was used to analyze the expression of 5α‐R in rat CP during aging. The obtained results demonstrated that 5α‐R expression is up‐regulated in 9 and 12 month‐old male rats (P<0,005), which may be associated with the reduced testosterone production observed in animals of these ages1 . In order to obtain information on the 5α‐R activity, we have performed ex vivo cultures of CP and monitored by thin layer chromatography the conversion of [3H]‐T into [3H]‐DHT. The CP tissue displayed no significant conversion of [3H]‐T to [3H]‐DHT, although results are not conclusive. Further work is necessary to confirm the activity of 5α‐R in CP. 1. Zirkin et. al (1997). Leydig cell steroidogenesis in aging rats. Exp. Gerontol. 32 (4‐ 5):529‐37.
The enzyme 5α‐reductase (5α‐R) metabolizes testosterone (T) to an active androgen, 5α‐dihydrotestosterone (DHT), in pheripheral tissues, including several brain regions. Recently our research group demonstrated the presence of 5α‐R mRNA in rat choroid plexus (CP). CP is responsible for the production of cerebrospinal fluid and also displays neuroprotective capabilities. During the aging process the CP shows a decline in all aspects of its function, which may increase the risk for development of neurodegenerative diseases. The presence of 5α‐R in CP suggests that androgens production may occur locally in this organ. However, there are no studies directed to the characterization of 5α‐R activity or to the identification of factors that regulate its expression in CP. In order to start clarifying these issues the following objectives were delineated: i) to confirm the presence of 5α‐R protein in rat CP; ii) to study the expression of 5α‐R during aging; iii) to demonstrate the bioactivity of 5α‐R in CP. Immunohistochemistry and Western blot analysis confirmed the presence of 5α‐R protein in rat CP. CPs were removed from male and female rats at different postnatal ages (3, 6, 9 and 12 month‐old), total RNA was extracted and used for cDNA synthesis. Real‐time PCR was used to analyze the expression of 5α‐R in rat CP during aging. The obtained results demonstrated that 5α‐R expression is up‐regulated in 9 and 12 month‐old male rats (P<0,005), which may be associated with the reduced testosterone production observed in animals of these ages1 . In order to obtain information on the 5α‐R activity, we have performed ex vivo cultures of CP and monitored by thin layer chromatography the conversion of [3H]‐T into [3H]‐DHT. The CP tissue displayed no significant conversion of [3H]‐T to [3H]‐DHT, although results are not conclusive. Further work is necessary to confirm the activity of 5α‐R in CP. 1. Zirkin et. al (1997). Leydig cell steroidogenesis in aging rats. Exp. Gerontol. 32 (4‐ 5):529‐37.
Description
Keywords
Plexo coróide Enzima 5a-reductase Androgénio - Envelhecimento
Citation
Publisher
Universidade da Beira Interior