Saníger Marcela Arrazola, Ramírez-Expósito María Jesús, de la Chica Susana, Carrera-González María Pilar, Mayas María Dolores, Manuel Martínez-Martos José
Experimental and Clinical Physiopathology Research Group. Department of Health Sciences, Faculty of Experimental and Health Sciences, University of Jaén, Jaén, Spain.
Drug Metab Lett. 2011 Aug;5(3):192-6. doi: 10.2174/187231211796905035.
Oxytocin (OT) is one of the important paracrine factors that prostate synthesizes. OT maintains its resting tone and stimulates its contractile activity. However, the involvement of OT in modulating cell proliferation of the prostate is being investigated. In fact, alterations in OT concentrations accompany both benign prostatic hyperplasia/hypertrophy and carcinoma of the prostate. The enzyme Insulin-regulated aminopeptidase (IRAP) is the main responsible of OT levels regulation through its catabolism. To date, the long-acting selective α(1)-adrenergic receptor antagonist doxazosin is widely used to the treatment of BPH. Thus, our aim was to analyze the effects of doxazosin on IRAP specific activity and its putative effects on prostate OT regulation and functions.
Fifteen male Wistar rats were treated subcutaneously with 10 mg/Kg doxazosin during 15 days and fifteen controls were treated with the vehicle only. After the treatment period, prostate was removed to obtain soluble and membrane-bound fractions. Soluble and membrane-bound IRAP specific activities were assayed fluorometrically using leucyl-ß-naphthylamide as substrate. Prostate OT content was assayed by enzyme immunoassay.
Doxazosin treatment significantly increased membrane-bound IRAP specific activity in rat prostate by 59.4%, whereas no changes were observed in the soluble fraction. Treatment with doxazosin also significantly increased OT concentration by 26.3%.
In vivo administration of doxazosin to male rats modify both prostatic IRAP activity and OT levels. Because there is now evidence that OT plays a physiological role in the regulation of growth and muscular contractility within the gland, more attention should be paid to IRAP activity, which could represent a new target for the regulation of the functions of OT under physiological or pathological conditions such as BPH and prostate cancer.
催产素（OT）是前列腺合成的重要旁分泌因子之一。OT维持其静息张力并刺激其收缩活动。然而，OT在调节前列腺细胞增殖中的作用正在研究中。事实上，OT浓度的改变在良性前列腺增生/肥大和前列腺癌中均有出现。胰岛素调节氨肽酶（IRAP）是通过其分解代谢调节OT水平的主要因素。迄今为止，长效选择性α（1）-肾上腺素能受体拮抗剂多沙唑嗪被广泛用于治疗良性前列腺增生。因此，我们的目的是分析多沙唑嗪对IRAP比活性的影响及其对前列腺OT调节和功能的假定作用。
15只雄性Wistar大鼠皮下注射10mg/Kg多沙唑嗪，持续15天，15只对照大鼠仅注射溶剂。治疗期结束后，取出前列腺以获得可溶性和膜结合部分。使用亮氨酰-β-萘酰胺作为底物，通过荧光法测定可溶性和膜结合IRAP的比活性。通过酶免疫测定法测定前列腺OT含量。
多沙唑嗪治疗使大鼠前列腺中膜结合IRAP比活性显著增加59.4%，而可溶性部分未观察到变化。多沙唑嗪治疗也使OT浓度显著增加26.3%。
对雄性大鼠体内给予多沙唑嗪可改变前列腺IRAP活性和OT水平。由于现在有证据表明OT在调节腺体内生长和肌肉收缩方面发挥生理作用，因此应更多关注IRAP活性，它可能代表在生理或病理条件如良性前列腺增生和前列腺癌下调节OT功能的新靶点。
