女性黄体孕激素产生的丧失与通过糖缀合物上的α2,6-唾液酸化的半乳糖凝集素开关有关。
The loss of luteal progesterone production in women is associated with a galectin switch via α2,6-sialylation of glycoconjugates.
机构信息
Medical Research Council Centre for Reproductive Health (J.N.-K., L.B., W.C.D.), The Queen's Medical Research Institute, The University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom; Creative Research Institution (M.A.), Hokkaido University, Sapporo 001-0021, Japan; and Laboratory of Histology and Cytology (J.N.-K., T.I.), Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
出版信息
J Clin Endocrinol Metab. 2014 Dec;99(12):4616-24. doi: 10.1210/jc.2014-2716.
CONTEXT
Luteal progesterone is fundamental for reproduction, but the molecular regulation of the corpus luteum (CL) in women remains unclear. Galectin-1 and galectin-3 bind to the sugar chains on cells to control key biological processes including cell function and fate.
METHODS
The expression and localization of LGALS1 and LGALS3 were analyzed by quantitative PCR and histochemical analysis, with special reference to α2,6-sialylation of glycoconjugates in carefully dated human CL collected across the menstrual cycle and after exposure to human chorionic gonadotrophin (hCG) in vivo. The effects of hCG and prostaglandin E2 on the expression of galectins and an α2,6-sialyltransferase 1 (ST6GAL1) in granulosa lutein cells were analyzed in vitro.
RESULTS
Galectin-1 was predominantly localized to healthy granulosa lutein cells and galectin-3 was localized to macrophages and regressing granulosa lutein cells. Acute exposure to luteotrophic hormones (hCG and prostaglandin E2) up-regulated LGALS1 expression (P < .001). ST6GAL1, which catalyzes α2,6-sialylation to block galectin-1 binding, increased during luteolysis (P < .05) as did LGALS3 (P < .05). Luteotrophic hormones reduced ST6GAL1 and LGALS3 in vivo (P < .05) and in vitro (P < .001). There was an inverse correlation between the expression of ST6GAL1 and HSD3B1 (P < .01) and a distinct cellular relationship among α2,6-sialylation, 3β-hydroxysteroid dehydrogenase, and galectin expression.
CONCLUSIONS
Galectin-1 is a luteotrophic factor whose binding is inhibited by α2,6-sialylation in the human CL during luteolysis. ST6GAL1 and galectin-3 expression is increased during luteolysis and associated with a loss of progesterone synthesis. Luteotrophic hormones differentially regulate galectin-1 and galectin-3/α2,6-sialylation in granulosa lutein cells, suggesting a novel galectin switch regulated by luteotrophic stimuli during luteolysis and luteal rescue.
背景
黄体孕激素对生殖至关重要，但女性黄体（CL）的分子调控仍不清楚。半乳糖凝集素-1 和半乳糖凝集素-3 与细胞上的糖链结合，以控制包括细胞功能和命运在内的关键生物学过程。
方法
通过定量 PCR 和组织化学分析分析 LGALS1 和 LGALS3 的表达和定位，特别参考了整个月经周期和体内暴露于人绒毛膜促性腺激素（hCG）后仔细标记的人类 CL 中糖缀合物的α2,6-唾液酸化。分析了 hCG 和前列腺素 E2 对体外颗粒黄体细胞中半乳糖凝集素和α2,6-唾液酰基转移酶 1（ST6GAL1）表达的影响。
结果
半乳糖凝集素-1 主要定位于健康的颗粒黄体细胞，半乳糖凝集素-3 定位于巨噬细胞和退化的颗粒黄体细胞。急性暴露于黄体营养激素（hCG 和前列腺素 E2）可上调 LGALS1 表达（P <.001）。催化α2,6-唾液酸化以阻断半乳糖凝集素-1 结合的 ST6GAL1 在黄体溶解过程中增加（P <.05），LGALS3 也是如此（P <.05）。黄体营养激素在体内（P <.05）和体外（P <.001）降低了 ST6GAL1 和 LGALS3 的表达。ST6GAL1 与 HSD3B1 的表达呈负相关（P <.01），并且α2,6-唾液酸化、3β-羟甾脱氢酶和半乳糖表达之间存在明显的细胞关系。
结论
半乳糖凝集素-1 是一种黄体营养因子，其在黄体溶解过程中与人类 CL 中的α2,6-唾液酸化结合受到抑制。ST6GAL1 和半乳糖凝集素-3 的表达在黄体溶解过程中增加，并与孕激素合成的丧失有关。黄体营养激素在颗粒黄体细胞中差异调节半乳糖凝集素-1 和半乳糖凝集素-3/α2,6-唾液酸化，提示黄体溶解和黄体挽救期间受黄体营养刺激调节的新型半乳糖开关。
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