Effects of castration and androgen replacement on erectile function in a rabbit model.
Effects of castration and androgen replacement on erectile function in a rabbit model.
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DOI：
10.1210/endo.140.4.6655
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发表时间：
1999-04
期刊：
影响因子：
4.8
通讯作者：
A. Traish;Kwangsung Park;Vinita Dhir;Noel N Kim;R. Moreland;I. Goldstein
中科院分区：
文献类型：
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作者：
A. Traish;Kwangsung Park;Vinita Dhir;Noel N Kim;R. Moreland;I. Goldstein
在兔模型中，我们研究了阉割和睾酮替代对海绵体血流动力学的影响：1)海绵体血流动力学；2) α -1肾上腺素能受体蛋白表达；3)神经NO合成酶蛋白表达与活性；4)磷酸二酯酶5型活性；5)小梁平滑肌/结缔组织平衡。双侧睾丸切除术后1周，动物单独用载药、睾酮或雌二醇治疗7天。完整的对照动物只接受载药。测量海绵体神经电刺激前后各动物的全身动脉血和海绵体内压（ICP）。通过配体结合研究测定α 1-肾上腺素能受体蛋白的表达。Western blot检测NO合成酶的表达和活性，l -精氨酸转化为瓜氨酸。在不含或存在100 nM西地那非的情况下，通过水解组织提取物中的鸟苷3',5'-环单磷酸（cGMP）来测定5型磷酸二酯酶的活性。通过马松三色染色和计算机辅助组织形态测定法评估平滑肌含量。阉割显著降低颅内压，但在刺激海绵体神经时没有改变全身动脉血压。睾酮治疗，而不是雌二醇治疗，阻止了阉割的影响，并将ICP恢复到与完整动物相似的值。去势降低了α 1-肾上腺素能受体的表达，这种降低被睾酮替代阻止或逆转。神经NO合成酶蛋白表达和总活性在去势和睾酮替代后均无显著改变。然而，用睾酮治疗的去势动物的磷酸二酯酶5型活性增加。去势显著降低小梁平滑肌含量，睾酮（而不是雌二醇）治疗恢复了这种减少。本研究结果表明，雄激素剥夺改变了勃起组织的功能反应和结构。
We investigated, in a rabbit model, the effects of castration and testosterone replacement on: 1) the hemodynamics of the corpus cavernosum; 2) alpha-1 adrenergic receptor protein expression; 3) neural NO synthase protein expression and activity; 4) phosphodiesterase type 5 activity; and 5) trabecular smooth muscle/connective tissue balance. One week after bilateral orchiectomy, animals were treated for 7 days with vehicle alone, testosterone, or estradiol. Intact control animals received vehicle only. Systemic arterial blood and intracavernosal pressures (ICP) were measured in each animal before and after electrical stimulation of the cavernosal nerve. Alpha1-adrenergic receptor protein expression was determined by ligand binding studies. NO synthase expression and activity were determined by Western blot analyses and conversion of L-arginine to citrulline, respectively. Phosphodiesterase type 5 activity was determined by hydrolysis of guanosine 3',5'-cyclic monophosphate (cGMP) in tissue extracts in the absence or presence of 100 nM sildenafil. Smooth muscle content was assessed by Masson's trichrome staining and computer-assisted histomorphometry. Castration significantly reduced ICP, but it did not alter systemic arterial blood pressure during stimulation of the cavernosal nerve. Testosterone, but not estradiol, treatment prevented the effects of castration and restored ICP to values similar to those obtained in intact animals. Castration reduced expression of alpha1-adrenergic receptor, and this reduction was prevented or reversed by testosterone replacement. Neural NO synthase protein expression and total activity were not altered significantly by castration or after testosterone replacement. However, phosphodiesterase type 5 activity increased in castrated animals treated with testosterone. Castration significantly reduced trabecular smooth muscle content, and this reduction was restored by testosterone (but not estradiol) treatment. The results of this study demonstrate that androgen deprivation alters the functional responses and structure of erectile tissue.