Cloning of cDNAs encoding the three pituitary glycoprotein hormone beta subunit precursor molecules in the Japanese...

Complementary DNAs encoding precursor molecules of the beta subunits of three pituitary glycoprotein hormones (LH, FSH, and TSH) of the Japanese toad (Bufo japonicus) were isolated and sequenced. Unexpectedly large numbers of single nucleotide substitutions were found in all three beta subunit cDNAs. The eight isolated LH beta precursor cDNA clones were classified into six forms of nucleotide sequence, with four nucleotide substitutions each in the apoprotein coding region and in the 3' untranslated region (UTR). In the deduced amino acid sequence, the LH beta subunit showed two forms with a single amino acid substitution. The seven isolated FSH beta subunit cDNAs were classified into two forms, which differed from each other at 11 positions in the 3' UTR. The six isolated TSH beta subunit clones were classified into four forms with 2 and 5 nucleotide substitutions in the signal peptide and apoprotein coding regions, respectively. However, all the substitutions in the apoprotein coding region were silent. The substitution in the signal peptide coding region could produce three forms of signal peptide. Amino acid sequence comparison revealed that the toad LH beta subunit is more similar to the fish GTH II beta subunit than to mammalian and avian LH beta subunits. We found that the toad LH beta subunit molecule is a partial chimera of LH and FSH; amino acid residues located in 36th to 42nd and 96th to 99th are identical or similar to those of not LH- but FSH-beta subunit in mammalian, whereas it is more similar to LH- than FSH-beta subunit in total. We also found that the toad FSH beta subunit is more similar to the fish GTH II beta subunit than to the fish GTH I beta subunit and that the toad TSH beta subunit is more similar to tetrapod TSH beta subunits than to fish TSH beta subunits.