Testicular interstitial cells as targets for peripheral benzodiazepines.
We evaluated the 'in vitro' effect of a selective peripheral benzodiazepine (BZD) receptor agonist, Ro 5-4864, on basal and hCG-stimulated androgen production by testicular interstitial cell suspensions. Ro 5-4864 (10(-9)-10(-5) M) induced a significant increment of basal testosterone release into the medium. In addition, under conditions of hCG stimulation, Ro 5-4864 (10(-7) M) induced a potentiated response to the gonadotropin in a dose-dependent manner. The selective peripheral BZD antagonist PK 11195 fully prevented the stimulatory effect of Ro 5-4864. On the other hand, clonazepam, a central BZD agonist, failed to affect androgen production significantly, whereas diazepam (10(-5)-10(-4) M), which binds to both central and peripheral BZD receptors, was able to induce a significant increment of basal and hCG-stimulated testosterone production. These results suggest that under our experimental conditions Ro 5-4864 exerts an effect on testicular steroidogenesis, presumably through binding to the previously described peripheral-type BZD receptor.
Ritta
M N
MN
Instituto de Biología y Medicina Experimental, Buenos Aires, Argentina.
Calandra
R S
RS
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D002998:Clonazepam / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology*; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000096:biosynthesis*
D001570:Benzodiazepinones; D007546:Isoquinolines; C028513:4'-chlorodiazepam; D013739:Testosterone; D002998:Clonazepam; D003975:Diazepam; C037850:PK 11195