Steroid 5alpha reductase mRNA type 1 is differentially regulated by androgens and glucocorticoids in the rat liver.
Testosterone and 5alpha-dihydrotestosterone (DHT) are the principal male hormones (androgens) in mammals. The enzyme, steroid 5alpha reductase catalyzes the conversion of testosterone (T) to its biologically potent steroid (DHT) in androgen dependent tissues. Two 5alpha 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 5alpha reductase type I (5alphaR1) messenger RNA in the rat liver were examined. Steady state levels of 5alphaR1 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 5alphaR1 to twice its' normal values within 40 hours. Bilateral orchiectomy induced, within eight days, the expression of 5alphaR1 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 microM) to primary cultures of rat hepatocyte resulted in a five- and three-fold reduction in the mRNA expression of 5alphaR1 after 24 and 48 hours, respectively. DHT (0.5 microM) however, induced the expression of 5alphaR1 mRNA by two- and seven-fold 24 and 48 hours post-treatment, respectively. In vitro nuclear run-on analysis of the 5alphaR1 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 5alphaR1 mRNA in the rat liver. Moreover, our findings appear to indicate that regulation of 5alphaR1 gene is primarily at the post-transcriptional level.
Department of Biomedical Technology, National Research Center, Cairo, Egypt.
Mostafa K
MK
El-Awady
Wael
W
El-Garf
Lamia
L
El-Houssieny
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics*; D000315:Adrenalectomy; D000728:Androgens / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology / Q000502:physiology*; D022781:Hepatocytes / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000728:Androgens; D005938:Glucocorticoids; D007527:Isoenzymes; D012333:RNA, Messenger; D003907:Dexamethasone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase