EXPRESSION OF PROLACTIN AND GROWTH-HORMONE RECEPTOR GENES AND THEIR ISOFORMS IN THE GASTROINTESTINAL-TRACT

Distribution of transcripts for prolactin and growth hormone receptors (PRLR and GHR) and their isoforms was characterized in the gastrointe stinal (GI) tract from several species by reverse transcription-polyme rase chain reaction combined with Southern analysis. Human, rabbit, an d fetal and adult rat PRLR and GHR transcripts were detected in isolat ed gastric glands, gastric cell fractions, and intestinal mucosa linea ges. Human PRLR and GHR transcripts were also observed throughout the cancerous progression of the colonic and gastric mucosa from adenomas to colonic liver metastasis and gastrointestinal cancer cell lines at various stages of growth and differentiation. Prolactin (PRL) produced no detectable effect on M1 gastric mucin secretion in HT-29 cells ada pted to methotrexate (HT-29-MTX) or on acid secretion in isolated rabb it parietal cells. GHRd3, an isoform of human GHR transcript missing e xon 3, was also broadly expressed and was the only form found in gastr ic and colorectal adenocarcinomas. Interestingly, several extra bands of polymerase chain reaction products of the human PRLR, which were sm aller than the expected size, were observed not only in the GI tract b ut also in liver and T-47D breast cancer cells. These products from hu man intestinal and breast cancer cell lines were subsequently subclone d and sequenced, and we isolated six isoforms of the receptor transcri pts. One of these clones encodes a putative human PRL binding protein. The expression of PRL and PRLR transcripts was also clearly observed in intraepithelial lymphocytes purified from the mouse intestine. The widespread expression of the PRL and GH receptor transcripts in gastri c and intestinal mucosal lineages, particularly in epithelia, suggests regulatory roles of these hormones on digestive and immune functions, including metabolism, growth, or differentiation.