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Isolation, Characterization, and Developmental Expression of the Rat Peptide-YY Gene

New England Medical Center Hospital, Tufts University School of Medicine Boston, Massachusetts 02111

Address requests for reprints to: Andrew B. Leiter, M.D., Ph.D., Division of Gastroenterology, #218, New England Medical Center, 750 Washington Street, Boston, Massachusetts 02111.

Abstract

In the present study we describe the isolation, structural characterization, and developmental expression of the gene encoding the intestinal hormone peptide-YY. Examination of the nucleotide sequence of the peptide-YY gene reveals that each of the four exons encodes a functional domain of its mRNA that is analogous to the corresponding exons of the genes encoding two closely related peptides neuropeptide-Y and pancreatic polypeptide. The highly conserved structural organization of the genes encoding this family of three peptides suggests that each gene arose from the duplication of a common ancestral gene. Developmental studies reveal that the peptide-YY gene exhibits a complex pattern of tissue-specific expression in the gastrointestinal tract. Unlike many gastrointestinal hormones, peptide-YY mRNA levels are highest before birth. The pancreas appears to be the major site of peptide-YY gene expression in the fetus, exceeding colonic expression by 7-fold. The abundance of peptide-YY mRNA in the pancreas declines rapidly after birth, in contrast to the colon, where mRNA levels are maintained throughout development into adulthood. Expression of the peptide-YY gene before birth antedates the presence of known enteral secretagogues for this hormone, suggesting alternate mechanisms that control its biosynthesis during development.

FOOTNOTES

This work was supported by NIH Grant DK-39209 and Grant P30-AM-39428 from the Center for Gastroenterology Research on Absorptive and Secretory Processes.

^* Recipient of the American Gastroenterological Association/William H. Rorer Industry Scholar Award.

Received for publication December 6, 1990. Revision received January 11, 1991. Accepted for publication January 11, 1991.

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