MOLECULAR PROBING OF THE SECRETORY PATHWAY IN PEPTIDE HORMONE-PRODUCING CELLS

The biosynthetic machinery in the melanotrope cells of the Xenopus int ermediate pituitary is primarily dedicated to the generation of proopi omelanocortin (POMC)-derived, melanophore-stimulating peptides. Transf er of the animal to a black background stimulates the production of th ese peptides and causes a dramatic increase in POMC mRNA levels. To id entify genes involved in the biosynthesis and regulated release of pep tide hormones, we differentially screened an intermediate pituitary cD NA library of toads adapted to a black background with cDNA probes der ived from intermediate pituitary mRNA of black- and white-adapted anim als. Here we report the identification of twelve distinct genes whose expression levels in the melanotropes are regulated in coordination wi th that of POMC. Four of these genes are novel while the others code f or translocon-associated proteins, a lumenal cysteine protease of the endoplasmic reticulum, prohormone-processing enzymes, members of the g ranin family and a transmembrane protein presumably involved in the as sembly and/or specific functioning of vacuolar H+-ATPase from secretor y granules, Our results indicate that a wide variety of both soluble a nd membrane-associated components of the secretory pathway is recruite d in physiologically activated, peptide hormone-producing cells.