Ritta M N, Calandra R S
Instituto de Biología y Medicina Experimental, Buenos Aires, Argentina.
Neuroendocrinology. 1989 Mar;49(3):262-6. doi: 10.1159/000125126.
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.
我们评估了一种选择性外周苯二氮䓬(BZD)受体激动剂Ro 5-4864对睾丸间质细胞悬液基础状态及人绒毛膜促性腺激素(hCG)刺激下雄激素生成的“体外”效应。Ro 5-4864(10⁻⁹ - 10⁻⁵ M)可使培养基中基础睾酮释放量显著增加。此外,在hCG刺激条件下,Ro 5-4864(10⁻⁷ M)能以剂量依赖方式增强对促性腺激素的反应。选择性外周BZD拮抗剂PK 11195可完全阻断Ro 5-4864的刺激作用。另一方面,中枢性BZD激动剂氯硝西泮对雄激素生成无显著影响,而既能与中枢又能与外周BZD受体结合的地西泮(10⁻⁵ - 10⁻⁴ M)能够使基础状态及hCG刺激下的睾酮生成显著增加。这些结果表明,在我们的实验条件下,Ro 5-4864可能通过与先前描述的外周型BZD受体结合,对睾丸类固醇生成产生影响。