Testicular 3 beta-hydroxysteroid dehydrogenase/delta 5-4 isomerase in the hypophysectomized rat: effect of treatment with 5 alpha-dihydrotestosterone.
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.
Fanjul
L F
LF
Departamento de Endocrinologia Celular y Molecular, Facultad de Medicina, Universidad de Las Palmas de Gran Canaria, Spain.
Quintana
J
J
González
J
J
Santana
P
P
Estévez
F
F
Ruiz de Galarreta
C M
CM
D000728:Androgens / Q000502:physiology; D000818:Animals; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007016:Hypophysectomy; D008297:Male; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011375:Progesterone Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013251:Steroid Isomerases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013737:Testis / Q000201:enzymology*
C021425:3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase; D000728:Androgens; D009097:Multienzyme Complexes; D013196:Dihydrotestosterone; D011375:Progesterone Reductase; D013251:Steroid Isomerases