FSH is a pituitary
gonadotropin that is encoded by separate alpha- and beta-subunit genes. We isolated a 12 kilobase (kb)
DNA fragment containing the entire
human FSH beta gene from a lambda phage genomic DNA library. The nucleotide sequence of the
FSH beta gene predicts
a 19 amino acid signal sequence and a 111
amino acid apoprotein that differs from the reported
protein sequence at three residues and lacks the carboxyterminal eight
amino acids, thereby bringing the
human FSH beta sequence into register with those described for other mammalian species. Southern blot analyses of human genomic
DNA are consistent with a single copy of the
FSH beta gene per haploid genome. The
FSH beta transcriptional unit spans 3.9 kb and contains two introns. The second intron (1.4 kb) is located between
amino acids 35 and 36, a position that is strictly conserved among all of the
glycoprotein hormone beta-subunit genes. The first intron occurs 6 base pairs upstream from the start of translation in a location analogous to that of the
TSH beta gene. The first exon contains an alternate splicing donor site resulting in 5'-untranslated sequences of 63 (Exon IA) and 33 (Exon IB) bases in length. Approximately 65% of transcripts contain exon IA and 35% contain exon IB. Two different polyadenylation sites are also used. One polyadenylation site coincides with the stop
codon, while the other site, which is used in greater than 80% of
FSH beta mRNA transcripts, is located approximately 1 kb downstream, resulting in an unusually long 3'-untranslated sequence. The distribution of polyadenylation sites is similar for
FSH beta mRNAs containing either Exons IA or IB suggesting that intron processing and polyadenylation are regulated independently. Thus, at least four distinct species of
FSH beta mRNA transcripts, all encoding identical
peptides, are processed from a single
FSH beta gene. The distribution of different
FSH beta mRNAs is similar in normal human pituitary tissue and several different FSH producing
pituitary adenomas.