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未受刺激的睾丸间质细胞中的氯离子外流会导致自主产生环磷酸腺苷(cAMP),并通过外流抑制剂刺激/抑制类固醇生成。

Chloride efflux in unstimulated Leydig cells causes autonomous cAMP production and stimulatory/inhibitory steroidogenesis with an efflux inhibitor.

作者信息

Panesar Nirmal S, Chan Kam W

机构信息

Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Whales Hospital, 1/F Clinical Sciences Building, 30-32 Ngan Shing Street, Shatin, New Territories, Hong Kong SAR, PR China.

出版信息

Steroids. 2005 Aug;70(9):652-9. doi: 10.1016/j.steroids.2005.03.010.

DOI:10.1016/j.steroids.2005.03.010
PMID:15913686
Abstract

Gonadotropins cause immediate chloride secretion in Leydig cells, which still have an unknown physiological. Thyroid and Leydig cells produce more cAMP and steroids, respectively, under low or chloride-free conditions. Here, we show that chloride efflux mediated by incubation of Mouse Leydig Tumor cells (MLTC-1) in hypotonic or chloride-free isotonic buffers results in more cAMP production without any gonadotropic stimulation. MLTC-1 cells incubated with 0.5mM diphenylamine-2-carboxylate (DPC), a chloride efflux inhibitor, produced increased amounts of testosterone as chloride ions were substituted by gluconate or sulphate ions under isotonic conditions. There was also an up-regulation of steroidogenic acute regulatory protein and 3beta-hydroxysteroid dehydrogenase/isomerase type I mRNAs, without human chorionic gonadotropin. With the exception of cAMP production, 2mM DPC inhibited all of the above, including the transcription of constitutively expressed cholesterol side-chain cleavage enzyme and the L19 house-keeping gene. Although it was speculated that gonadotropin mediated chloride secretion could aid steroid hormone release, we conclude that the real reason for chloride secretion in Leydig cells may be to "kick start" cAMP production.

摘要

促性腺激素可使睾丸间质细胞立即分泌氯离子,其生理作用尚不清楚。在低渗或无氯条件下,甲状腺细胞和睾丸间质细胞分别产生更多的环磷酸腺苷(cAMP)和类固醇。在此,我们发现,将小鼠睾丸间质瘤细胞(MLTC-1)置于低渗或无氯等渗缓冲液中孵育介导的氯离子外流,在没有任何促性腺激素刺激的情况下会产生更多的cAMP。在等渗条件下,用0.5mM二苯胺-2-羧酸盐(DPC,一种氯离子外流抑制剂)孵育MLTC-1细胞,随着氯离子被葡萄糖酸盐或硫酸盐离子取代,睾酮分泌量增加。在没有人类绒毛膜促性腺激素的情况下,类固醇生成急性调节蛋白和I型3β-羟基类固醇脱氢酶/异构酶的mRNA也上调。除了cAMP的产生外,2mM DPC抑制了上述所有情况,包括组成型表达的胆固醇侧链裂解酶和L19管家基因的转录。尽管有人推测促性腺激素介导的氯离子分泌可能有助于类固醇激素释放,但我们得出结论,睾丸间质细胞中氯离子分泌的真正原因可能是“启动”cAMP的产生。

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