Abstract. Testosterone and 5a-dihydrotestosterone (DHT) are the principal male hormones (androgens) in mammals. The enzyme, steroid 5a reductase catalyzes the conversion of testosterone (T) to its biologically potent steroid (DHT) in androgen dependent tissues. Two 5a 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 5a reductase type I (5aR1) messenger RNA in the rat liver were examined. Steady state levels of 5aR1 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 5aR1 to twice its' normal values within 40 hours. Bilateral orchiectomy induced, within eight days, the expression of 5aR1 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 mM) to primary cultures of rat hepatocyte resulted in a five-and three-fold reduction in the mRNA expression of 5aR1 after 24 and 48 hours, respectively. DHT (0.5 mM) however, induced the expression of 5aR1 mRNA by two-and seven-fold 24 and 48 hours post-treatment, respectively. In vitro nuclear run-on analysis of the 5aR1 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 5aR1 mRNA in the rat liver. Moreover, our findings appear to indicate that regulation of 5aR1 gene is primarily at the post-transcriptional level. TESTOSTERONE and dihydrotestosterone (DHT) are the major circulating androgens in humans and other vertebrates. Although each hormone displays potent effects in biological assays of androgen action, under specific conditions, each hormone displays properties that suggest roles in the modulation of specific functions. It is clear that DHT is crucial for the normal development of the male genitalia and of the prostate [1,2]. In contrast, testosterone appears to play essential roles in promoting spermatogenesis and Wollfian duct development, as well as gonadotropin regulation. The steroid 5a reductase enzyme plays an important physiological role in the conversion of testosterone to its bioactive and reduced derivatives; 5a dihydrotestosterone (DHT) in androgen dependent tissues [3]. To date, two steroid 5a reductase isoenzymes have been cloned and characterized in humans and rats. These isoenzymes are encoded by independent genes designated types I and II. In peripheral tissues such as the liver, type (I) 5a-reductase (5aR1) and reductive 3a-hydroxysteroid dehydrogenase (3a-HSD) isomers work consecutively to eliminate androgens and protect against hormone excess [4]. It has been postulated tha...