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Polymorphism of gonadotropin action:clinical implications

Polymorphism of gonadotropin action:clinical implications
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摘要 It has recently became apparent that the stmctural heterogeneity of gonadotropin molecules can contribute to varia-tions of their action in different physiological and pathophysiological conditions. One reason for the structural variationsof circulating gonadotropin molecules is the microheterogeneity caused by the variability of glycosylation of individualgonadotropin molecules. The carbohydrate moieties of gonadotropins are important for their intrinsic bioactivity, as re-flected by measurement of their bioactivity to immunoreactivity (B/I) ratios. We have reassessed this phenomenon byimproved in vitro bioassay and immunoassay methods, and it appears that the intrinsic bioactivity of gonadotropins, inparticular of LH, is more constant than previously assumed. Many of the previously documented differences, someeven considered diagnostic for certain clinical conditions, have tumed out to be methodological artifacts. The first partof this review summarizes our recent findings on the B/I ratios of LH, with special reference to the male. The second part of this review describes a common polymorphism that was recently discovered in the gene of theLH β-subunit. The variant LHβ allele contains two point mutations, which introduce to LH two amino acid changes andan extra glycosylation site. The LH variant is common world-wide, with carrier frequency varying from 0 to 52% invarious ethnic groups. The LH variant differs functionally from wild-type LH, and it seems to predispose its carders,both men and women, to mild aberrations of reproductive function. It is important for the clinician to be aware of thisvariant LH form, not detected by all immunoassays, because it may explain some aberrant results of LH measurementsin patient samples. (Asian J Androl 2000 Dec; 2: 241-246) It has recently became apparent that the stmctural heterogeneity of gonadotropin molecules can contribute to varia-tions of their action in different physiological and pathophysiological conditions. One reason for the structural variationsof circulating gonadotropin molecules is the microheterogeneity caused by the variability of glycosylation of individualgonadotropin molecules. The carbohydrate moieties of gonadotropins are important for their intrinsic bioactivity, as re-flected by measurement of their bioactivity to immunoreactivity (B/I) ratios. We have reassessed this phenomenon byimproved in vitro bioassay and immunoassay methods, and it appears that the intrinsic bioactivity of gonadotropins, inparticular of LH, is more constant than previously assumed. Many of the previously documented differences, someeven considered diagnostic for certain clinical conditions, have tumed out to be methodological artifacts. The first partof this review summarizes our recent findings on the B/I ratios of LH, with special reference to the male. The second part of this review describes a common polymorphism that was recently discovered in the gene of theLH β-subunit. The variant LHβ allele contains two point mutations, which introduce to LH two amino acid changes andan extra glycosylation site. The LH variant is common world-wide, with carrier frequency varying from 0 to 52% invarious ethnic groups. The LH variant differs functionally from wild-type LH, and it seems to predispose its carders,both men and women, to mild aberrations of reproductive function. It is important for the clinician to be aware of thisvariant LH form, not detected by all immunoassays, because it may explain some aberrant results of LH measurementsin patient samples. (Asian J Androl 2000 Dec; 2: 241-246)
出处 《Asian Journal of Andrology》 SCIE CAS CSCD 2000年第4期241-246,共6页 亚洲男性学杂志(英文版)
关键词 LH FSH BIOASSAY immunometric assay mutation POLYMORPHISM GLYCOSYLATION LH FSH bioassay immunometric assay mutation polymorphism glycosylation
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