Blomquist J F, Baenziger J U
Department of Pathology, Washington University Medical School, St. Louis, Missouri 63110.
J Biol Chem. 1992 Oct 15;267(29):20798-803.
The glycoprotein hormones lutropin (LH) and follitropin (FSH) are both synthesized by gonadotrophs in the anterior pituitary but are stored in separate secretory granules prior to secretion. Despite having highly homologous beta-subunits and alpha-subunits with the identical amino acid sequence, the Asn-linked oligosaccharides on LH terminate with SO4-GalNAc while those on FSH terminate with sialic acid-Gal. In addition to LH and FSH, gonadotrophs secrete uncombined (free) alpha-subunit which bears the same sulfated oligosaccharides as LH. We have examined the synthesis and secretion of LH and free alpha-subunit in primary cultures of bovine pituitary cells in order to determine if the sulfated oligosaccharides have any impact on sorting. Our results show that newly synthesized free alpha-subunit is secreted exclusively via the constitutive pathway with a t1/2 of 1.8 h and is never found in dense-core secretory granules. In contrast, LH dimer is secreted by both the constitutive and the regulated pathways. Constitutive secretion and arrival in a dense secretory granule both occur with t1/2 values of 1-1.5 h for newly synthesized LH. Sulfation occurs immediately prior to arrival of LH in the secretory granule and is followed by a period of 1-1.5 h before the LH-containing granules become sensitive to release by gonadotropin releasing hormone. As a result the t1/2 for LH secretion in the presence of gonadotropin releasing hormone is 3.5 h. Sulfation of the free alpha-subunit oligosaccharides is not, therefore, sufficient to direct the alpha-subunit to secretory granules, and the information required for directing LH to granules must reside either in the beta-subunit or the alpha beta-complex.
糖蛋白激素促黄体生成素（LH）和促卵泡生成素（FSH）均由垂体前叶的促性腺激素细胞合成，但在分泌前分别储存在不同的分泌颗粒中。尽管LH和FSH的β亚基和α亚基具有高度同源性且α亚基的氨基酸序列相同，但LH上的N-连接寡糖以硫酸化的N-乙酰半乳糖胺（SO4-GalNAc）结尾，而FSH上的则以唾液酸-半乳糖（sialic acid-Gal）结尾。除了LH和FSH，促性腺激素细胞还分泌未结合的（游离的）α亚基，其带有与LH相同的硫酸化寡糖。我们研究了牛垂体细胞原代培养物中LH和游离α亚基的合成与分泌，以确定硫酸化寡糖是否对分选有任何影响。我们的结果表明，新合成的游离α亚基仅通过组成型途径分泌，半衰期为1.8小时，从未在致密核心分泌颗粒中发现。相比之下，LH二聚体通过组成型途径和调节型途径分泌。新合成的LH通过组成型分泌并到达致密分泌颗粒的半衰期均为1-1.5小时。硫酸化在LH到达分泌颗粒之前立即发生，随后经过1-1.5小时，含LH的颗粒才对促性腺激素释放激素的释放变得敏感。因此，在存在促性腺激素释放激素的情况下，LH分泌的半衰期为3.5小时。因此，游离α亚基寡糖的硫酸化不足以将α亚基导向分泌颗粒，而将LH导向颗粒所需的信息必定存在于β亚基或αβ复合物中。
