Vagell M E, McGinnis M Y
Department of Cell Biology and Anatomy, Mount Sinai School of Medicine, City University of New York, NY 10029-6574, USA.
J Neuroendocrinol. 1997 Jun;9(6):415-21. doi: 10.1046/j.1365-2826.1997.00598.x.
This study assessed the role of aromatization in the expression of male reproductive behavior by testing the effects of the aromatase inhibitor, fadrozole, on the restoration of male sexual behavior and partner preference in testosterone-treated gonadectomized rats. We measured nuclear estrogen receptor occupation to determine whether fadrozole blocked brain aromatase. In addition, nuclear androgen receptor assays were used to verify that fadrozole does not block androgen receptors. Mini-osmotic pumps fitted to brain infusion cannulas were used to deliver fadrozole (20 micrograms/day) into the right lateral ventricle. The majority of animals receiving fadrozole treatment with two, 10 mm testosterone filled Silastic capsules (T/F group) failed to display any sexual behavior 7 and 13 days following implant surgery. In contrast, animals receiving fadrozole treatment which were implanted with two, 10 mm testosterone capsules and one, 5 mm 1% estradiol capsule (T/F/E group) copulated normally, indicating that fadrozole's inhibition of male sex behavior was specifically due to blocking aromatase activity. Moreover, the animals which received only one, 5 mm 1% estradiol capsule (E group) also failed to exhibit male sexual behavior. Partner preference for either a sexually receptive female or a non-receptive female was measured in a three chambered apparatus for an index of sexual motivation. Repeated measures contrasts on the group x test interaction indicated that the T/F group was not significantly different from the T group. In addition, the E group did not show a preference for the receptive females and was significantly different from the T group. Fadrozole treatment resulted in a 59% decrease in brain nuclear estrogen receptor occupation relative to the T group. Fadrozole had no significant effect on brain nuclear androgen receptor occupation. Our results lend support to the hypothesis that both androgen receptor activation and aromatization are necessary for the restoration of male sexual behavior in rats. However, we found that estradiol is neither necessary nor sufficient for the restoration of partner preference.
本研究通过测试芳香化酶抑制剂法倔唑对经睾酮处理的去势大鼠雄性性行为恢复和配偶偏好的影响，评估了芳香化作用在雄性生殖行为表达中的作用。我们测量了核雌激素受体占有率，以确定法倔唑是否阻断脑芳香化酶。此外，还采用了核雄激素受体测定法来验证法倔唑不会阻断雄激素受体。将微型渗透泵安装在脑内灌注插管上，用于将法倔唑（20微克/天）输送到右侧脑室。大多数接受法倔唑治疗并植入两个10毫米睾酮填充硅橡胶胶囊的动物（T/F组）在植入手术7天和13天后未表现出任何性行为。相比之下，接受法倔唑治疗并植入两个10毫米睾酮胶囊和一个5毫米1%雌二醇胶囊的动物（T/F/E组）正常交配，表明法倔唑对雄性性行为的抑制作用具体是由于阻断了芳香化酶活性。此外，仅接受一个5毫米1%雌二醇胶囊的动物（E组）也未表现出雄性性行为。在三室装置中测量对性接受雌鼠或非接受雌鼠的配偶偏好，作为性动机指标。对组×测试交互作用的重复测量对比表明，T/F组与T组无显著差异。此外，E组对接受雌鼠无偏好，且与T组有显著差异。与T组相比，法倔唑治疗使脑内核雌激素受体占有率降低了59%。法倔唑对脑内核雄激素受体占有率无显著影响。我们的结果支持了这样的假设，即雄激素受体激活和芳香化作用对于大鼠雄性性行为的恢复都是必要的。然而，我们发现雌二醇对于配偶偏好的恢复既非必要条件也非充分条件。
