Developmental and hormonal regulation of the monocarboxylate transporter 2 (MCT2) expression in the mouse germ cells

Developmental and hormonal regulation of the monocarboxylate transporter 2 (MCT2) expression in the mouse germ cells
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DOI:
10.1095/biolreprod.102.010074
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发表时间:
2003-09-01
影响因子:
3.6
通讯作者:
Benahmed, M
Benahmed, M
中科院分区:
生物学2区
文献类型:
--
作者:
Boussouar, F;Mauduit, C;Benahmed, M

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在精子发生过程中,减数分裂后的生殖细胞利用支持细胞产生的乳酸作为能量代谢产物。虽然支持细胞中乳酸产生的激素调节已经相对完善,但这种能量底物向生殖细胞的转运,特别是通过单羧酸转运蛋白(MCT),以及这种过程的潜在内分泌控制仍有待表征。在这里,我们报告的发育和生殖调控的睾丸中的MCT 2的表达。在第18天,如通过北方印迹检测到的,MCT 2开始在生殖细胞中表达。mRNA在精子细胞中翻译成蛋白质(40 kDa)。超微结构分析表明,MCT 2蛋白定位于精子细胞尾部的细胞膜外表面。MCT 2 mRNA水平受内分泌(特别是促卵泡激素(FSH)和睾酮)和旁分泌系统的控制。事实上,35日龄大鼠垂体切除导致睾丸MCT 2 mRNA水平增加8倍。相反,垂体切除大鼠接受FSH和LH给药后,MCT 2 mRNA水平降低至在完整动物中观察到的基础水平。使用FSH或睾酮孵育的离体生精小管在体外证实了MCT 2 mRNA水平的降低。FSH或睾酮以剂量依赖性方式抑制MCT 2 mRNA水平,FSH和睾酮的最大抑制剂量分别为2.2 ng/ml和55.5 ng/ml。除内分泌控制外,TNF α和TGF β还对MCT 2 mRNA水平产生抑制作用,TGF β和TNF α的最大作用分别为10 ng/ml和6.6 ng/ml。与以前的研究一起,目前的数据加强了这一概念,即睾丸内分泌/旁分泌系统的关键功能之一是控制支持细胞-生殖细胞代谢合作背景下发生的能量代谢,其中乳酸在体细胞中产生并至少通过MCT 2转运到生殖细胞。
During spermatogenesis, postmeiotic germ cells utilize lactate produced by Sertoli cells as an energy metabolite. While the hormonal regulation of lactate production in Sertoli cells has been relatively well established, the transport of this energy substrate to the germ cells, particularly via the monocarboxylate transporters (MCTs), as well as the potential endocrine control of such a process remain to be characterized. Here, we report the developmentally and hormonally regulated expression of MCT2 in the testis. At Day 18, MCT2 starts to be expressed in germ cells as detected by Northern blot. The mRNA are translated into protein (40 kDa) in elongating spermatids. Ultrastructural analysis demonstrated that MCT2 protein is localized to the outer face of the cell membrane of spermatid tails. MCT2 mRNA levels are under the control of the endocrine, specifically follicle-stimulating hormone (FSH) and testosterone, and paracrine systems. Indeed, a 35-day-old rat hypophysectomy resulted in an 8-fold increase in testicular MCT2 mRNA levels. Conversely, FSH and LH administration to the hypophysectomized rats reduced MCT2 mRNA levels to the basal levels observed in intact animals. The decrease in MCT2 mRNA levels was confirmed in vitro using isolated seminiferous tubules incubated with FSH or testosterone. FSH or testosterone inhibited in a dose-dependent manner MCT2 mRNA levels with maximal inhibitory doses of 2.2 ng/ml and 55.5 ng/ml for FSH and testosterone, respectively. In addition to the endocrine control, TNFalpha and TGFbeta also exerted an inhibitory effect on MCT2 mRNA levels with a maximal effect at 10 ng/ml and 6.6 ng/ml for TGFbeta and TNFalpha, respectively. Together with previous studies, the present data reinforce the concept that among the key functions of the endocrine/paracrine systems in the testis is the control of the energy metabolism occurring in the context of Sertoli cell-germ cell metabolic cooperation where lactate is produced in somatic cells and transported to germ cells via, at least, MCT2.