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Human Follicle-Stimulating Hormone β-Subunit Gene Encodes Multiple Messenger Ribonucleic Acids

Thyroid Unit and Laboratory of Molecular Endocrinology, Massachusetts General Hospital and Howard Hughes Medical Institute, Harvard Medical School Boston, Massachusetts 02114

Address requests for reprints to: J. Larry Jameson, M.D., Ph.D., Thyroid Unit, Bulfinch Basement, Massachusetts General Hospital, Boston, Massachusetts 02114.

Abstract

FSH is a pituitary gonadotropin that is encoded by separate - and β-subunit genes. We isolated a 12 kilobase (kb) DNA fragment containing the entire human FSHβ gene from a phage genomic DNA library. The nucleotide sequence of the FSHβ 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 FSHβ 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 FSHβ gene per haploid genome. The FSHβ 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 β-subunit genes. The first intron occurs 6 base pairs upstream from the start of translation in a location analogous to that of the TSHβ 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 FSHβ mRNA transcripts, is located approximately 1 kb downstream, resulting in an unusually long 3'-untranslated sequence. The distribution of polyadenylation sites is similar for FSHβ mRNAs containing either Exons IA or IB suggesting that intron processing and polyadenylation are regulated independently. Thus, at least four distinct species of FSHβ mRNA transcripts, all encoding identical peptides, are processed from a single FSHβ gene. The distribution of different FSHβ mRNAs is similar in normal human pituitary tissue and several different FSH producing pituitary adenomas.

FOOTNOTES

The human FSHβ nucleotide sequence is assigned accession number M18536 in The Genbank data base. This work was supported by PHS Grants HD-23262 (to J.L.J.) and DK-25532 (to J.F.H.) and by support from the Chugai and Upjohn Awards.

Received for publication March 25, 1988. Accepted for publication May 16, 1988.

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