| Budget Amount *help |
¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
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| Research Abstract |
Although polymorphism in the LHβ gene variant with a mutant β-subunit (Trp8 to Arg8 and Ile15 to Thr15) is commonly found in most population, the clinical consequences of carrying this LH variant are still unclear. To elucidate the effect of an luteinizing hormone (LH) variant on ovulation and reproductive mechanism and to evaluate its significance in gynecologic disease, including infertility, serum samples were collected from healthy non-pregnant Japanese women and patients with gynecologic disease and DNA from blood cells was studied in patients using polymerase chain reaction and direct sequencing. In immunoassays, results with a monoclonal antibody recognizing only the wild-type hormone (SPAC-S LH) and a polyclonal antibody recognizing the variant (Immulyze LH) as well were compared as a ratio (LH ratio : SPAC-S LH/Immulyze LH) and 0.50 was considered a "cut-off" value for identifying individuals with the variant. We conclude that measuring serum LH with specific immunoassay syste
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ms can distinguish subjects with variant from those with normal LH in screening for the mutant LHβ gene. Using the ratio of KH values from these assays to determine variant (<ィイD2-ィエD20.5) or wild-type (>0.5) LH status ratio, the variant occurred more frequently in the patients with gynecologic disease (18.4%) than in healthy women (8.5%). The variant was more frequent in patients with ovulatory disorders (43.8%) than other patients (16.0%). Premature ovarian failure, hyperprolactinemia and luteal insufficiency were significantly more frequent in patients with the variant. Variant LH may contribute to female reproductive disorder, including infertility and premature ovarian failure. To assess the secretion of variant LH on pituitary stimulation than wild-type LH, since in serum variant LH showed a more rapid increase and reached a higher apparent concentration than the wild-type hormone.
Furethermore, we confirmed that subjects who were homozygous for mutant LHβ-subunit showed an excessive LH response in the GnRH stimulation test, similar to the response in patients with PCOS. However, this response pattern from variant LH did not show a relationship to ovulatory disorders. Therefore, the biologic effects and clinical significance of variant LH require much further investigation. Less
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