Testicular 3β-hydroxysteroid dehydrogenase/Δ^5-4 isomerase in the hypophysectomized rat: Effect of treatment with 5α-dihydrotestosterone

Abstract

The in-vivo regulatory effect of androgens on steroidogenesis was investigated. Adult (2 to 3 months old) hypophysectomized rats were treated intratesticularly with increasing doses of 5-alpha-dihydrotestosterone (DHT; 10-200-mu-g/100 g body weight) or vehicle (50-mu-l dimethyl sulphoxide; DMSO) in the contralateral testis. Intratesticular testosterone concentrations were extremely low in hypophysectomized rats 15-20 days after surgery. Treatment with DHT caused a dose-dependent inhibition of testicular 3-beta-hydroxysteroid dehydrogenase/DELTA-(5-4) isomerase (3-beta-HSD) 2 h later, and this effect was apparent at the dose of 20-mu-g/100 g body weight (P < 0.01). The inhibitory effect of 3-beta-HSD was not due to a possible interference of DHT in the enzyme assay, since various concentrations of the androgen (0.1-100-mu-mol/l) were ineffective as inhibitors of 3-beta-HSD. The highest dose of DHT used in this study (200-mu-g/100 g body weight) resulted in a rapid (1-2 h) and transient (4-6 h) inhibition (approximately 80%) of 3-beta-HSD activity. Pretreatment of rats with the antiandrogen cyproterone acetate (5 mg/rat) or the protein synthesis inhibitor cycloheximide (10 mg/rat) did not affect the enzyme activity of testes injected with DMSO, but counteracted the inhibitory effect of DHT on 3-beta-HSD activity in the contralateral testis. The results presented suggest that the inhibitory effect of the non-aromatizable androgen DHT is receptor-mediated and involves the synthesis of a factor(s) that modulates 3-beta-HSD activity.