Lessons from the gonadotropin-regulated long chain acyl-CoA synthetase (GR-LACS) null mouse model: a role in steroidogenesis, but not result in X-ALD phenotype.
Lessons from the gonadotropin-regulated long chain acyl-CoA synthetase (GR-LACS) null mouse model: a role in steroidogenesis, but not result in X-ALD phenotype.
复制标题
促性腺激素调节的长链酰基辅酶 A 合成酶 (GR-LACS) 无效小鼠模型的教训：在类固醇生成中发挥作用，但不会导致 X-ALD 表型。
DOI：
10.1016/j.jsbmb.2008.12.011
复制
发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Dufau,MariaL
中科院分区：
文献类型：
--
作者：
Sheng,Yi;Tsai-Morris,Chon-Hwa;Li,Jie;Dufau,MariaL
促性腺激素调节的长链脂肪酸酰基辅酶A合成酶（GR-LACS）是拉克家族的一员，在大鼠睾丸间质细胞（LC）中受促性腺激素调节。它的小鼠/人类同源物，阿糖胞苷/泡泡糖，已被认为参与X-连锁肾上腺脑白质营养不良（X-ALD），一种肾上腺/神经退行性疾病，在组织和血浆中积累极长链脂肪酸（VLCFA）。为了进一步深入了解其调节功能，产生了GR-LACS/阿糖胞苷缺失小鼠。在X-ALD靶组织（脑、睾丸、肾上腺）中未观察到明显的表型异常。在>15月龄小鼠中观察到的核包涵体存在于9月龄GR-LACS−/−小鼠的LC中。无效小鼠的LC表现出对在成年动物中观察到的促性腺激素诱导的睾酮产生脱敏的不应性。睾丸、卵巢和大脑中的LCFA中度增加，但GR-LACS−/−小鼠的肾上腺中没有，VLCFA没有重大变化。在这些组织中没有观察到拉克活性的变化，这表明其他拉克成员表现出的代偿机制。GR-LACS−/−模型不支持它与X-ALD的关联。这些研究揭示了GR-LACS在减少LC老化过程中的作用，以及其参与促性腺激素诱导的睾丸睾酮产生脱敏。
Gonadotropin-regulated long chain fatty acid Acyl-CoA synthetase (GR-LACS), is a member of the LACS family that is regulated by gonadotropin in the rat Leydig cell (LC). Its mouse/human homologs, lipidosin/bubblegum, have been suggested to participate in X-linked adrenoleukodystrophy (X-ALD), an adreno/neurodegenerative disorder with accumulation of very long chain fatty acids (VLCFA) in tissues and plasma. To further gain insights into its regulatory function, a GR-LACS/lipidosin null mouse was generated. No apparent phenotypic abnormalities were observed in the X-ALD target tissues (brain, testis, adrenal). Nuclear inclusions seen in mice >15 month-old, were present in LC of 9 month-old GR-LACS−/−mice. LC of the null mice showed refractoriness to the gonadotropin-induced desensitization of testosterone production that is observed in adult animals. LCFAs were moderately increased in the testis, ovary and brain, but not in the adrenal gland of GR-LACS−/−mice, with no major changes in VLCFA. No change in LACS activity was observed in these tissues, suggesting a compensatory mechanism exhibited by other LACS members. The GR-LACS−/−model did not support its association with X-ALD. These studies revealed a role of GR-LACS in reducing the aging process of the LC, and its participation in gonadotropin-induced testicular desensitization of testosterone production.