Pearl Christopher A, Boime Irving
Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, United States.
Mol Cell Endocrinol. 2009 Oct 15;309(1-2):76-81. doi: 10.1016/j.mce.2009.03.004. Epub 2009 Mar 20.
LH and FSH are produced by the same gonadotrope cells of the anterior pituitary but differ in their mode of secretion. LH secretion is primarily episodic, or regulated, while FSH secretion is primarily basal, or constitutive. The asparagine (N)-linked oligosaccharides of LH and FSH terminate with sulfate and sialic acid, respectively. TSH also contains sulfated N-linked oligosaccharides and is secreted through the regulated pathway. It has been hypothesized that sulfate plays a role in segregating LH to the regulated pathway. Using a mouse pituitary model, we tested this hypothesis by examining the secretory fate of LH from pituitaries treated with sodium chlorate, a known inhibitor of sulfation. Here we show that mouse LH is sulfated and secreted through the regulated pathway, while FSH is secreted constitutively. LH secretion from chlorate-treated pituitaries, which showed complete inhibition of sulfation, was similar to untreated pituitaries. These data suggest that the metabolic role for sulfated N-linked oligosaccharides is not for intracellular trafficking but for the extracellular bioactivity of LH.
促黄体生成素(LH)和促卵泡生成素(FSH)由腺垂体相同的促性腺激素细胞产生,但分泌方式不同。LH的分泌主要是阵发性的,即受调节的,而FSH的分泌主要是基础的,即组成型的。LH和FSH的天冬酰胺(N)连接寡糖分别以硫酸盐和唾液酸结尾。促甲状腺激素(TSH)也含有硫酸化的N连接寡糖,并通过受调节的途径分泌。据推测,硫酸盐在将LH分离到受调节的途径中起作用。利用小鼠垂体模型,我们通过检查用氯酸钠(一种已知的硫酸化抑制剂)处理的垂体中LH的分泌命运来验证这一假设。我们在此表明,小鼠LH被硫酸化并通过受调节的途径分泌,而FSH则组成型分泌。氯酸盐处理的垂体中LH的分泌显示硫酸化完全受到抑制,这与未处理的垂体相似。这些数据表明,硫酸化的N连接寡糖的代谢作用不是用于细胞内运输,而是用于LH的细胞外生物活性。