Related Experiment Videos
Structural and functional characterisation of hFSH and hLH isoforms
P G Stanton1, P G Burgon, M T Hearn
1Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia.
Molecular and Cellular Endocrinology
|December 20, 1996
Summary
Structural variations in human follicle-stimulating hormone (hFSH) and human luteinizing hormone (hLH) isoforms contribute to their differing biological functions. Sialic acid content significantly influences hormone activity and clearance rates.
Area of Science:
- Endocrinology
- Reproductive Biology
- Biochemistry
Background:
- Human pituitary gonadotropins, follicle-stimulating hormone (hFSH) and luteinizing hormone (hLH), exist as multiple isoforms.
- These isoforms exhibit structural and functional heterogeneity, impacting their biological roles.
Purpose of the Study:
- To investigate the structural and functional heterogeneity of purified hFSH and hLH isoforms.
- To determine the correlation between isoform structure, receptor activity, and in vivo bioactivity.
Main Methods:
- Purification of hFSH and hLH isoforms using isoelectric focusing and ion-exchange chromatography.
- Characterization of isoforms by amino acid analysis, SDS-PAGE, and HPLC.
- Assays for radioreceptor activity, in vitro bioactivity, circulating half-life, and in vivo bioactivity.
Main Results:
- A significant range in hFSH receptor activity and hLH in vivo bioactivity was observed across different isoforms.
- Sialic acid content positively correlated with FSH receptor activity and circulating half-life.
- In vitro and in vivo activities of hLH isoforms showed good correlation, with clearance rates potentially impacting chronic responses.
Conclusions:
- Structural heterogeneity of hFSH and hLH isoforms directly contributes to functional differences.
- Hormone-receptor interaction is a key determinant of biological activity.
- Sialic acid content plays a crucial role in modulating gonadotropin activity and pharmacokinetics.