Functional characterization of a natural variant of luteinizing hormone.
Luteinizing hormone (LH) plays an important role in the gametogenesis in both sexes by promoting the production of sex steroid hormones in the testes and ovaries. We previously described a genetic variant (V) of LH resulted from a mutation (G1502A) in the LH beta-subunit gene, causing the glycine102serine change in the protein hormone. This variant was subsequently found to be associated with both male and female infertility. In this study, we determined the functional aspect of this LH variant in vitro. Site-directed mutagenesis was employed to construct the V-LH beta-subunit gene. Bioactivities of V-LH expressed in Chinese hamster ovary (CHO) cells cotransfected with the V-beta-subunit and native alpha-subunit genes were compared to those of wild-type (WT) LH. The amino acid replacement did not result in the change of efficacy of alpha- and beta-subunit dimerization of the hormone. However, V-LH had significantly lower receptor-binding activity (P<0.001) and lower biopotency for progesterone production (P<0.001) than WT-LH at the higher concentrations of LH. Considering the latter and its known association with both male and female infertility, it is suggested that the V-LH may be a contributing factor to the pathogenesis of infertility in the carriers of this variant.
Department of Obstetrics and Gynaecology, National University of Singapore, National University Hospital, Lower Kent Ridge Road, Singapore 119074.
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Liao
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Goh
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Roy
D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D006224:Cricetinae; D017931:DNA Primers / Q000737:chemistry; D014644:Genetic Variation; D006801:Humans; D066298:In Vitro Techniques; D007986:Luteinizing Hormone / Q000235:genetics* / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D016133:Polymerase Chain Reaction; D011233:Precipitin Tests; D011374:Progesterone / Q000378:metabolism; D011974:Receptors, LH / Q000378:metabolism; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D014162:Transfection
D017931:DNA Primers; D011974:Receptors, LH; D011994:Recombinant Proteins; D011374:Progesterone; D007986:Luteinizing Hormone