Steroid 5.ALPHA. Reductase mRNA Type I is Differentially Regulated by Androgens and Glucocorticoids in the Rat Liver

Accession number;04A0170019
Title;Steroid 5.ALPHA. Reductase mRNA Type I is Differentially Regulated by Androgens and Glucocorticoids in the Rat Liver
Author; EL-AWADY M K (National Res. Center, Cairo, Egy) EL-GARF W (National Res. Center, Cairo, Egy) EL-HOUSSIENY L (National Res. Center, Cairo, Egy)
Journal Title;Endocr J
Journal Code:F0625A
ISSN:0918-8959
VOL.51;NO.1;PAGE.37-46(2004)
Figure&Table&Reference;FIG.4, REF.44
Pub. Country;Japan
Language;English
Abstract;Testosterone and 5.ALPHA.-dihydrotestosterone (DHT) are the principal male hormones (androgens) in mammals. The enzyme, steroid 5.ALPHA. reductase catalyzes the conversion of testosterone (T) to its biologically potent steroid (DHT) in androgen dependent tissues. Two 5.ALPHA. reductase isoenzymes have been identified in rat tissues. The type I isoenzyme has been shown to be predominately expressed in the rat liver, whereas androgen target tissues of the genital tract express mainly isoenzyme II. The effects of androgens and glucocorticoids on the abundance of steroid 5.ALPHA. reductase type I (5.ALPHA.R1) messenger RNA in the rat liver were examined. Steady state levels of 5.ALPHA.R1 mRNA decreased dramatically to 1.5% of control levels 14 days following adrenalectomy (ADX), whereas dexamethasone (Dex) administered (0.5 mg/100 g) to ADX animals enhanced the expression of 5.ALPHA.R1 to twice its' normal values within 40 hours. Bilateral orchiectomy induced, within eight days, the expression of 5.ALPHA.R1 mRNA in the rat liver to 1.75 fold the normal value while testosterone injection failed to reduce this enhanced expression in castrated animals. Addition of Dex (1 .MU.M) to primary cultures of rat hepatocyte resulted in a five- and three-fold reduction in the mRNA expression of 5.ALPHA.R1 after 24 and 48 hours, respectively. DHT (0.5 .MU.M) however, induced the expression of 5.ALPHA.R1 mRNA by two- and seven-fold 24 and 48 hours post-treatment, respectively. In vitro nuclear run-on analysis of the 5.ALPHA.R1 gene showed no correlation between the rate of synthesis and steady state levels of this mRNA either in the intact liver or in cultured hepatocytes. These results appear to suggest that glucocorticoids and androgens differentially regulate 5.ALPHA.R1 mRNA in the rat liver. Moreover, our findings appear to indicate that regulation of 5.ALPHA.R1 gene is primarily at the post-transcriptional level. (author abst.)
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