Regulation of steroidogenic enzymes and a novel testicular RNA helicase.
Regulation of steroidogenic enzymes and a novel testicular RNA helicase.
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类固醇生成酶的调节和新型睾丸 RNA 解旋酶。
DOI：
10.1016/s0960-0760(01)00051-6
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Khanum,A
中科院分区：
文献类型：
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作者：
Dufau,ML;Tsai-Morris,C;Tang,P;Khanum,A
黄体生成素（LH）支持类固醇生成和维持睾丸和卵巢功能。LH作用的介质对间质细胞（LC）的膜受体、甾体生成酶和其他可调节基因进行同源调控。LH诱导的雄激素和雌激素可通过其在LC中的同源受体调控基因表达。虽然雄激素在精子发生中是必不可少的，并且可能通过存在于睾丸中的雄激素受体发挥其异源作用，但其在生殖细胞成熟中的调节机制尚不清楚。与生理浓度的促性腺激素相比，促性腺激素维持性腺的类固醇生成功能和LH和催乳素受体，高浓度的促性腺激素（hCG）导致体内LCs的类固醇生成酶（3β-羟基类固醇脱氢酶I型和II型，17α-羟化酶/17,20水解酶和17β-羟基类固醇脱氢酶III型[17β- hsd]）的受体下调和脱敏。此外，17β-HSD受区隔化的内源性葡萄糖/ATP调控。甾体生成的减弱是由于受体介导的同源激素激活，但独立于受体下调的后续阶段，是由于转录水平的变化。影响这一调节的候选者包括活性类固醇代谢物（直接或间接的类固醇和其他介质，如cAMP， LH作用诱导的推定转录因子）。差异显示试验揭示了另一个受促性腺激素转录调控的基因，称为促性腺激素调节睾丸解旋酶（GRTH）。GRTH是DEAD-box RNA解旋酶家族的新成员，在睾丸LC和减数分裂LC中特异性表达。hCG通过camp诱导的LCs雄激素形成，在一定剂量下导致受体和甾体生成酶下调，从而显著上调LCs的雄激素水平。GRTH起着翻译激活剂的作用。促性腺激素刺激产生的雄激素对GRTH具有分泌/自分泌作用，并可影响精管内的转录。GRTH可能有助于控制甾体形成，包括恢复下调的细胞功能，以及参与减数分裂过程的雄激素依赖基因的旁分泌调节，因此可能在精子发生中起关键作用。
Luteinizing hormone (LH) supports steroidogenesis and maintains testicular and ovarian function. Mediators of LH action exert homologous regulation of membrane receptors, steroidogenic enzymes and other regulatable genes of the Leydig cell (LC). Androgen and estrogen induced by LH could act through its cognate receptors in the LC to regulate gene expression. Although androgens are unquestionable essential for spermatogenesis and presumably exert their heterologous action through androgen receptors present in the Sertoli its regulatory mechanism in germinal cell maturation is far from clear. In contrast to physiological concentrations of gonadotropins which maintain the steroidogenic functions and LH and prolactin receptors in the gonads, high concentrations of gonadotropin (hCG) cause receptor down-regulation and desensitization of steroidogenic enzymes of the LCs in vivo (3β-hydroxysteroid dehydrogenase types I and II, 17α-hydroxylase/17,20 lyase, and 17β-hydroxysteroid dehydrogenase type III [17β-HSD]). In addition, 17β-HSD is regulated by compartmentalized endogenous glucose/ATP. The attenuation of steroidogenesis which results from receptor mediated activation by cognate hormone, but is independent of the subsequent phase of receptor down-regulation, is due to changes at the transcriptional level. Among the candidates affecting this regulation are active steroid metabolites (direct or indirect of steroids and other mediator(s) i.e. cAMP, putative transcription factors induced by LH action). Differential display assay revealed another gene which is transcriptionally regulated by gonadotropin termed GRTH (Gonadotropin Regulated Testicular Helicase). GRTH is a novel member of the DEAD-box family of RNA helicases, and is specifically expressed in LCs and meiotic LC of the testis. It is markedly up-regulated by hCG via cAMP-induced androgen formation in LCs at doses that cause down-regulation of receptors and steroidogenic enzymes. GRTH functions as a translational activator. Androgen produced by gonadotropin stimulation exerts intracrine/autocrine actions on GRTH, and also could influence transcription within the seminiferous tubule. GRTH may contribute to the control of steroidogenesis, including the restoration of down regulated cellular functions, and in the paracrine regulation of androgen dependent gene(s) involved in the meiotic process, and could thus have a crucial role in spermatogenesis.