心房利钠因子在分离的小鼠睾丸间质细胞中的类固醇生成作用由环磷酸鸟苷介导。
Steroidogenic effect of atrial natriuretic factor in isolated mouse Leydig cells is mediated by cyclic GMP.
作者信息
Mukhopadhyay A K, Schumacher M, Leidenberger F A
出版信息
Biochem J. 1986 Oct 15;239(2):463-7. doi: 10.1042/bj2390463.
The effects of different atrial natriuretic peptides on cyclic GMP formation and steroidogenesis have been studied in Percoll-purified mouse Leydig cells. Rat atrial peptides rANP (rat atrial natriuretic peptide), rAP-I (rat atriopeptin I) and rAP-II (rat atriopeptin II), in the presence of a phosphodiesterase inhibitor, stimulated cyclic GMP formation in a concentration-dependent manner. In the presence of saturating concentrations of the peptides, a 400-600 fold stimulation of cyclic GMP accumulation was observed. Among the peptides, rAP-II appeared to be the most potent. ED50 values (concentration causing half-maximal effect) for rAP-II, rANP and rAP-I were 1 X 10(-9) M, 2 X 10(-9) M and 2 X 10(-8) M respectively. A parallel stimulation of cyclic GMP formation and testosterone production by the cells was observed after incubation of the cells with various concentrations of rAP-II. In the presence of a saturating concentration of rAP-II (2 X 10(-8) M), maximum stimulation of intracellular cyclic GMP content was obtained within 5 min of incubation. Testosterone production by mouse Leydig cells could be stimulated by 8-bromo cyclic GMP in a concentration-related manner. At a 10 mM concentration of the cyclic nucleotide, steroidogenesis was stimulated to a similar extent as that obtained with a saturating concentration of human chorionic gonadotrophin (5 ng/ml). On the basis of these results we conclude that cyclic GMP acts as a second messenger in atrial-peptide-stimulated steroidogenesis in mouse Leydig cells. The steroidogenic effect of atrial peptides appears to be species-specific, since none of these peptides stimulated testosterone production by purified Leydig cells of rats, though in these cells a 40-60-fold stimulation of cyclic GMP formation in response to each of the three peptides was observed. However, 8-bromo cyclic GMP could stimulate testosterone production in rat Leydig cells. Therefore we conclude that the lack of steroidogenic response in rat Leydig cells to atrial-natriuretic-factor-stimulation results from an insufficient formation of cyclic GMP in these cells. This species difference would appear to result from a lower guanylate cyclase activity in rat Leydig cells.
在经Percoll纯化的小鼠睾丸间质细胞中，研究了不同心房利钠肽对环磷酸鸟苷（cGMP）生成和类固醇生成的影响。在磷酸二酯酶抑制剂存在的情况下，大鼠心房肽rANP（大鼠心房利钠肽）、rAP-I（大鼠心房肽I）和rAP-II（大鼠心房肽II）以浓度依赖的方式刺激cGMP生成。在肽浓度饱和时，观察到cGMP积累增加了400 - 600倍。在这些肽中，rAP-II似乎最有效。rAP-II、rANP和rAP-I的半数有效浓度（ED50值，即引起最大效应一半的浓度）分别为1×10⁻⁹ M、2×10⁻⁹ M和2×10⁻⁸ M。用不同浓度的rAP-II孵育细胞后，观察到细胞对cGMP生成和睾酮产生有平行刺激作用。在rAP-II浓度饱和（2×10⁻⁸ M）时，孵育5分钟内细胞内cGMP含量得到最大刺激。小鼠睾丸间质细胞的睾酮产生可被8-溴环磷酸鸟苷以浓度相关的方式刺激。在环核苷酸浓度为10 mM时，类固醇生成的刺激程度与用人绒毛膜促性腺激素饱和浓度（5 ng/ml）时相似。基于这些结果，我们得出结论，cGMP在心房肽刺激小鼠睾丸间质细胞类固醇生成过程中作为第二信使起作用。心房肽的类固醇生成作用似乎具有物种特异性，因为这些肽均未刺激大鼠纯化睾丸间质细胞产生睾酮，尽管在这些细胞中观察到对这三种肽中的每一种都有40 - 60倍的cGMP生成刺激。然而，8-溴环磷酸鸟苷可刺激大鼠睾丸间质细胞产生睾酮。因此我们得出结论，大鼠睾丸间质细胞对心房利钠因子刺激缺乏类固醇生成反应是由于这些细胞中cGMP生成不足。这种物种差异似乎是由于大鼠睾丸间质细胞中鸟苷酸环化酶活性较低所致。
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