睾丸在垂体-睾丸轴对一氧化氮相关因子反应中的作用。

Role of the testis in the response of the pituitary-testicular axis to nitric oxide-related agents.

作者信息

Gaytán F, Bellido C, Aguilar R, Morales C, van Rooijen N, Aguilar E

机构信息

Department of Cell Biology, School of Medicine, University of Córdoba, Spain.

出版信息

Eur J Endocrinol. 1997 Sep;137(3):301-8. doi: 10.1530/eje.0.1370301.

DOI:10.1530/eje.0.1370301

PMID:9330596

Abstract

Nitric oxide (NO) is generated from the guanidine group of L-arginine by NO synthases (NOS) in a wide variety of tissues, including endocrine organs. In order to discriminate between central and local effects of NO-related agents on the pituitary-testicular axis, adult rats were injected intraperitoneally with 1 g/kg body weight (bw) L-arginine methyl ester (L-AME, an exogenous substrate of NOS), 0.5 mg/kg bw sodium nitroprusside (SNP, an NO donor) or vehicle (0.9% NaCl) or intratesticularly with 2 mg/testis L-AME, 2 micrograms/testis SNP or 25 microliters vehicle, and killed at 60 or 120 min after treatment. Both intraperitoneal and intratesticular administration of L-AME had the same effects: a decrease in the serum concentrations of LH and testosterone and in those of testosterone in the testicular interstitial fluid. However, treatment with SNP was more effective when given intratesticularly, inducing a decrease in serum and interstitial fluid testosterone concentrations, without significant changes in LH concentrations. Furthermore, when rats were injected intraperitoneally with 4 mg L-AME (the same dose as that given intratesticularly), serum LH concentrations were not changed. In addition, L-AME administration was not effective in modifying serum LH concentrations in castrated rats. To test the possible role of Leydig cells, the effects of systemic administration of L-AME were studied in rats depleted of Leydig cells by treatment with ethylene dimethane sulphonate. In these animals L-AME significantly decreased serum LH concentrations. To study the role of macrophages in this system, rats depleted of testicular macrophages by the liposome-suicide approach were injected intraperitoneally (1 g/kg bw) or intratesticularly (2 mg/testis) with L-AME or vehicle, 10 days after macrophage depletion, and killed at 120 min after treatment. The effects of L-AME on serum LH concentrations were blocked when the drug was administered intratesticularly.

摘要

一氧化氮（NO）由一氧化氮合酶（NOS）作用于L-精氨酸的胍基，在包括内分泌器官在内的多种组织中生成。为了区分与NO相关的药物对垂体-睾丸轴的中枢和局部作用，给成年大鼠腹腔注射1 g/kg体重（bw）的L-精氨酸甲酯（L-AME，NOS的一种外源性底物）、0.5 mg/kg bw的硝普钠（SNP，一种NO供体）或溶剂（0.9%氯化钠），或者睾丸内注射2 mg/睾丸的L-AME、2 μg/睾丸的SNP或25 μl溶剂，并在处理后60或120分钟处死。腹腔和睾丸内给予L-AME产生相同的效果：血清促黄体生成素（LH）和睾酮浓度以及睾丸间质液中睾酮浓度降低。然而，睾丸内给予SNP更有效，可导致血清和间质液中睾酮浓度降低，而LH浓度无显著变化。此外，当给大鼠腹腔注射4 mg L-AME（与睾丸内注射剂量相同）时，血清LH浓度未改变。另外，给予L-AME对去势大鼠的血清LH浓度无影响。为了测试睾丸间质细胞的可能作用，研究了用乙烷二甲磺酸盐处理使睾丸间质细胞耗竭的大鼠经全身给予L-AME的效果。在这些动物中，L-AME显著降低了血清LH浓度。为了研究巨噬细胞在该系统中的作用，在巨噬细胞耗竭10天后，给采用脂质体自杀法使睾丸巨噬细胞耗竭的大鼠腹腔注射（1 g/kg bw）或睾丸内注射（2 mg/睾丸）L-AME或溶剂，并在处理后120分钟处死。当药物经睾丸内给药时，L-AME对血清LH浓度的作用被阻断。