Follicle-stimulating hormone sweetness: How carbohydrate structures impact on the biological function of the hormone

IF 4.7 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Alfredo Ulloa-Aguirre , Regina Llamosas , James A. Dias
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引用次数: 0

Abstract

Follicle-stimulating hormone (FSH), or follitropin, exists in multiple molecular forms due largely to its protein-carbohydrate composition and the complexity of the glycans attached to the protein core. The heterogeneity of gonadotropins exists in two forms, macroheterogeneity, which results from the absence of one or two oligosaccharide chains in the ß-subunit, and microheterogeneity which results from variation in the structures and complexity of the glycans attached to the hormone. In the clinical arena, FSH compounds are widely used by fertility specialists to promote ovarian follicle growth and maturation to a preovulatory follicle containing a fertilization-competent oocyte. Several genetically engineered recombinant human FSH preparations have been added to the arsenal of follitropin preparations in several countries for the treatment of infertility, particularly in women attending assisted reproduction clinics. Although the primary structure of these recombinant proteins is identical to that of naturally occurring FSH, the cell context and variations in the production and purification processes may impact the glycosidic profile of the recombinant FSH macro- and micro-heterogeneity, which may potentially influence the pharmacokinetics and pharmacodynamics of the compound. This review concentrates on the structure-function correlates of follitropin, with emphasis on the physiological and biological importance of the carbohydrates attached to its protein core, including its pharmacokinetics and biological activity. Emphasis is placed on pituitary FSH, and the available data on the various recombinant FSH preparations employed in therapeutics are also discussed, considering that this gonadotropin represents the cornerstone for the treatment of infertility in modern assisted reproduction.
促卵泡激素的甜味:碳水化合物结构如何影响激素的生物功能。
促卵泡激素(FSH)或称促性腺激素(follitropin)具有多种分子形式,这主要是由于其蛋白质-碳水化合物组成以及附着在蛋白质核心上的聚糖的复杂性。促性腺激素的异质性有两种形式,一种是大异质性,这是因为ß-亚基中缺少一个或两个寡糖链;另一种是微异质性,这是因为附着在激素上的聚糖的结构和复杂性不同。在临床上,生育专家广泛使用 FSH 复合物来促进卵泡生长和成熟,使其成为含有受精能力卵母细胞的排卵前卵泡。一些国家已将几种基因工程重组人 FSH 制剂添加到卵泡刺激素制剂库中,用于治疗不孕症,尤其是辅助生殖诊所的妇女。虽然这些重组蛋白的主要结构与天然存在的 FSH 相同,但细胞环境以及生产和纯化过程中的变化可能会影响重组 FSH 的糖苷谱宏观和微观异构体,从而可能影响化合物的药代动力学和药效学。这篇综述集中探讨了促绒毛膜促性腺激素的结构-功能相关性,重点是附着在其蛋白质核心上的碳水化合物在生理和生物学方面的重要性,包括其药代动力学和生物活性。考虑到垂体促性腺激素是现代辅助生殖中治疗不孕症的基石,本综述将重点放在垂体促性腺激素上,并讨论了治疗中使用的各种重组促性腺激素制剂的现有数据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Archives of Medical Research
Archives of Medical Research 医学-医学:研究与实验
CiteScore
12.50
自引率
0.00%
发文量
84
审稿时长
28 days
期刊介绍: Archives of Medical Research serves as a platform for publishing original peer-reviewed medical research, aiming to bridge gaps created by medical specialization. The journal covers three main categories - biomedical, clinical, and epidemiological contributions, along with review articles and preliminary communications. With an international scope, it presents the study of diseases from diverse perspectives, offering the medical community original investigations ranging from molecular biology to clinical epidemiology in a single publication.
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