Polymorphism of gonadotropin action: clinical implications

Area of Science:

• Endocrinology
• Molecular Biology
• Reproductive Medicine

Background:

• Gonadotropin structural heterogeneity, especially glycosylation, influences biological activity.
• Variations in bioactivity to immunoreactivity (B/I) ratios have been linked to physiological and pathophysiological states.
• Previous findings on gonadotropin B/I ratios may be attributed to methodological limitations.

Purpose of the Study:

• To reassess the intrinsic bioactivity of gonadotropins, focusing on luteinizing hormone (LH) in males.
• To investigate the impact of a common LH beta-subunit gene polymorphism on LH function and reproductive health.
• To inform clinicians about a variant LH form that may affect immunoassay results.

Main Methods:

• Utilized improved in vitro bioassay and immunoassay techniques to measure LH bioactivity.
• Reviewed recent findings on LH B/I ratios, with a focus on male subjects.
• Described the genetic and functional characteristics of a common LH beta-subunit gene variant.

Main Results:

• The intrinsic bioactivity of LH appears more constant than previously assumed, with many prior differences identified as methodological artifacts.
• A common LH beta-subunit gene variant, resulting from two point mutations and an extra glycosylation site, is prevalent globally.
• This LH variant exhibits altered function and may predispose carriers to mild reproductive function aberrations.

Conclusions:

• Re-evaluation suggests gonadotropin bioactivity is more consistent, challenging previous diagnostic interpretations.
• A common, functionally distinct LH variant exists worldwide and can impact reproductive function.
• Clinicians must be aware of this variant LH form, as it may not be detected by all immunoassays and can explain aberrant LH measurements.