Disparate response of wild-type and variant forms of LH to GnRH stimulation in individuals heterozygous for the LH beta variant allele

There is a common genetic variant of LH due to two amino acid changes in th e LH beta subunit, Trp(8)Arg and Ile(15)Thr. In order to compare the relati ve activities of wild type (wt-LH) and variant LH beta (nu -LH beta) genes in LH production and secretion, we performed gonadotrophin-releasing hormon e (GnRH) stimulation tests for healthy females (n = 7) and males (n = 10) h eterozygous for the nu -LH beta allele, Blood samples were drawn up to 180 min after injection of GnRH. The serum samples were subjected to two immuno fluorometric assays, one detecting wt hormone, the other detecting equally both LH types. The wt/total ratio increased significantly (P less than or e qual to 0.016) after GnRH injection in males. This indicates that the propo rtion of wt-LH increases in the circulation in men but not in women, and th at women consequently secrete relatively more v-LH. An in-vitro bioassay wa s performed on 0 and 60 min samples, and the bio/immunoreactivity (B/I) rat io decreased in both sexes (P = 0.010-0.012). This supports the previously reported lower B/I ratio of wt than v-LH, since wt-LH is expected to accumu late in circulation because of its longer half-life. In conclusion, these f indings demonstrate that wt- and v-LH respond differently to GnRH stimulati on in men and women heterozygous for nu -LH beta. These results are in agre ement with previously documented differences of the two forms in circulatio n, as well as with different promoter activities of the two LH beta alleles .