Stimulation of testosterone production in rat Leydig cells by aldosterone is mineralocorticoid receptor mediated
Stimulation of testosterone production in rat Leydig cells by aldosterone is mineralocorticoid receptor mediated
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DOI：
10.1016/j.mce.2005.08.004
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发表时间：
2005-11-24
影响因子：
4.1
通讯作者：
Hardy, MP
中科院分区：
文献类型：
--
作者：
Ge, RS;Dong, Q;Hardy, MP
已知睾丸是皮质酮作用的部位，糖皮质激素直接抑制睾丸间质细胞中睾酮的产生。糖皮质激素结合糖皮质激素受体（GR）和盐皮质激素受体（MR）。在Leydig细胞中，选择性盐皮质激素结合可能是由于糖皮质激素被1型和/或2型11 β-羟基类固醇脱氢酶（11 β HSD）氧化灭活，因为这两种亚型都表达。然而，目前尚不清楚间质细胞是否表达MR并直接对盐皮质激素的作用作出反应。因此，本研究的目的是确定：（1）是否MR mRNA，蛋白质和受体结合存在于Leydig细胞;（2）如果盐皮质激素调节睾酮的产生。在成年大鼠Leydig细胞中分别观察到编码MR的mRNA以及蛋白质和结合活性。通过测量在存在和不存在甘珀酸（11 β HSD 1和2的抑制剂，其降低生物惰性11-脱氢皮质酮的转化）的情况下皮质酮与醛固酮结合的MR置换，进一步评价了分离的Leydig细胞内的MR-配体结合特异性。甘珀酸抑制11 PHSD氧化活性，并减少皮质酮结合50%。在醛固酮（0.01-10 nM）存在下，在有或没有MR拮抗剂RU 28318的情况下，评估盐皮质激素对类固醇生成的影响。醛固酮诱导的基础和黄体生成素刺激的睾酮产生呈剂量依赖性增加。RU 28318消除了增加，表明醛固酮的这些作用是由MR介导的。醛固酮和黄体生成素（0.1 ng/ml）对睾酮产生的作用是协同的，表明这两种激素通过单独的途径增加类固醇生成。我们的结论是，睾丸间质细胞表达MR和睾酮的生产受到调节醛固酮。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
The testis is known to be a site of corticosterone action, and testosterone production in Leydig cells is directly inhibited by glucocorticoids. Glucocorticoids bind to both glucocorticoid receptors (GRs) and to mineralocorticoid receptors (MRs). In Leydig cells, selective mineralocorticoid binding could result from oxidative inactivation of glucocorticoid by type 1 and/or 2 11 beta-hydroxysteroid dehydrogenase (11 beta HSD), as both isoforms are expressed. However, it remains unclear whether Leydig cells express MRs and respond directly to mineralocorticoid action. Therefore, the aims of the present study were to ascertain: (1) whether MR mRNA, protein and receptor binding are present in Leydig cells; and (2) if the mineralocorticoid modulates testosterone production. The mRNA encoding MR, as well as protein, and binding activity were each observed in adult rat Leydig cells. MR-ligand binding specificity within isolated Leydig cells was evaluated further by measuring displacement of MR binding to aldosterone by corticosterone in the presence and absence of carbenoxolone, an inhibitor of 11 beta HSD1 and 2 that decreases conversion to biologically inert 11-dehydrocorticosterone. Carbenoxolone inhibited 11PHSD oxidative activity, and reduced corticosterone-binding by 50%. Mineralocorticoid effects on steroidogenesis were assessed in the presence of aldosterone (0.01-10 nM) with or without the MR antagonist, RU28318. Aldosterone induced dose-dependent increases in both basal and luteinizing hormone-stimulated testosterone production. RU28318 eliminated the increase, indicating that these effects of aldosterone were mediated by the MR. The effects of aldosterone and luteinizing hormone (0.1 ng/ml) on testosterone production were synergistic, suggesting that the two hormones increased steroidogenesis through separate pathways. We conclude that Leydig cells express MRs and that testosterone production is subject to regulation by aldosterone. (c) 2005 Elsevier Ireland Ltd. All rights reserved.