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

Area of Science:

• Endocrinology and Reproductive Biology
• Glycobiology
• Biochemistry

Background:

• Pituitary follitropin (FSH) exists as glycosylation variants affecting its biological activity.
• Sialylation patterns, particularly 2,3 vs. 2,6 linkage, influence FSH half-life by modulating liver asialoglycoprotein receptor (ASGPR) binding.
• FSH glycosylation on the β-subunit changes with age and impacts in vivo action, yet clinical data on preparations are scarce.

Purpose of the Study:

• To review the biochemical and structural aspects of follitropin glycosidic variability.
• To assess the potential impact of glycosylation differences on follitropin's biological function and clinical effects in humans.
• To highlight the need for open data and further research on recombinant FSH preparations.

Main Methods:

• Literature review focusing on biochemical and structural data of follitropin glycosylation.
• Analysis of published studies on FSH glycosylation, including in vitro assays and animal models.
• Discussion of glycosylation features like sialylation, sulfation, and fucose presence.

Main Results:

• High sialylation, especially 2,3-linked, is associated with longer FSH half-life by inhibiting ASGPR binding.
• Human 2,6-linked sialylation does not prevent ASGPR recognition, potentially leading to shorter half-life.
• Limited clinical data exist comparing outcomes from different commercially available FSH preparations regarding glycosylation.

Conclusions:

• Structural differences in FSH glycosylation, particularly sialylation, likely affect biological function and clinical outcomes.
• Further research, including clinical studies and open data sharing, is needed to elucidate the precise impact of FSH glycosylation variants.
• Understanding fucose's role and studying recombinant FSH preparations are critical future directions.