新型卵泡素製劑FSH：聚醣結構差異如何影響生化和生物學功能以及臨床效果

• 人工合成知FSH變體的1級~4級結構，包括糖基化差異。對於FSH知生化效果均產生不同效果
• 這些糖苷形式包括糖基化位點的數量、糖苷鏈的複雜性以及唾液酸化和硫酸化方面均有差異，
• 高唾液酸化，末端 N-乙酰半乳糖胺或半乳糖的 2,3 唾液酸封端通過阻斷肝臟中脫唾液酸糖蛋白受體 (ASGPR) 的結合，導致更長的循環半衰期。
• FSH 糖基化主要在 β 亞基上，隨著女性年齡的增長而變化，已成為FSH作用的關鍵修飾因子，在動物模型體內具有深遠的生物學效應。
•  FSH 在垂體中以兩個亞基的形式產生，一個是所有糖蛋白激素共有的亞基，即 α 亞基，另一個是每種激素特有的亞基，即 β 亞基。
• 尿液中的促卵泡素與天然垂體促卵泡素的不同之處在於其聚醣的程度和復雜性以及相關糖蛋白激素（黃體生成素）和其他蛋白質的污染
• FSH Alpha類包括   Gonal-F®、Bemfola®、Ovaleap® 、Cinnal-f®. 它是CHO細胞系生產的
• FSH Beta 類包括    Follistim® 和 Puregon®。它是CHO細胞系生產的
• Follitropin Delta 包括促卵泡素 Rekovelle®，它是使用人類細胞系生產的 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018285/

New Human Follitropin Preparations: How Glycan Structural Differences May Affect Biochemical and Biological Function and Clinical Effect

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1. Pituitary follitropin is secreted into the circulation as a mixture of variants, which differ not in primary structure but rather at the level of glycosylation. 
2. These glycosidic forms vary in the number of glycosylation sites filled, complexity of glycosidic chains, and sialylation and sulfation. 
3. high sialylation, 2,3 sialic acid capping of terminal N-acetyl galactosamine or galactose leads to longer circulating half-life, by blocking binding of asialoglycoprotein receptor (ASGPR) in the liver. 
4. FSH glycosylation, primarily on the β-subunit, which varies as women age, has emerged as a key modifier of follitropin action, with profound biological effects in vivo in animal models.
5.  FSH is produced in the pituitary gland as two subunits, one subunit common to all glycoprotein hormones, the α-subunit, and another subunit specific for each hormone, the β-subunit. 
6. . Follitropin in urine differed from naturally occurring pituitary follitropin in degree and complexity of their glycans and contamination with a related glycoprotein hormone (luteinizing hormone) and other proteins
7.  Recombinant follitropin Gonal-F®, and biosimilars Bemfola®, Ovaleap® and Cinnal-f® are grouped into one class called follitropin Alpha. 
8. The follitropin Beta class includes Follistim® and Puregon®. 
9. Follitropin Delta included the follitropin Rekovelle® which is produced using a human cell line and results in a product that possesses sialic acid2,6 as well as sialic acid2,3 capped Gal.