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 micrograms/100 g
body weight) or vehicle (50 microliters
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 micrograms/100 g
body weight (P less than 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 mumol/l) were ineffective as inhibitors of 3 beta-HSD. The highest dose of DHT used in this study (200 micrograms/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.