RESP18, A NOVEL ENDOCRINE SECRETORY PROTEIN TRANSCRIPT, AND 4 OTHER TRANSCRIPTS ARE REGULATED IN PARALLEL WITH PROOPIOMELANOCORTIN IN MELANOTROPES

The homogeneous nature of the rat intermediate pituitary makes it a po werful model system in which to study peptide hormone secretion. Adult male rats were treated with bromocriptine, a dopamine agonist, or hal operidol, a dopamine antagonist, for 3 weeks. In cDNA libraries prepar ed from the neurointermediate pituitaries of these rats, pro-opiomelan ocortin (POMC) expression exhibited the expected decrease in response to bromocriptine, and increase in response to haloperidol. We report t he identification of six transcripts that are coregulated with POMC in the intermediate pituitary by these dopaminergic agents. In addition to demonstrating parallel dopamine-regulated expression of carboxypept idase E, chromogranin B, binding protein/glucose-regulated protein, an d tenascin, two novel regulated transcripts are described. The express ion of one of these novel transcripts, RESP18, is limited to neural an d endocrine tissue. The RESP18 transcript is approximately 800 nucleot ides in length; its cognate translation product is 20 +/- 1 kDa, conta ins a putative signal sequence, and has many characteristics of a secr eted protein. Cell-free translation experiments in the presence of mic rosomal membranes demonstrate that the 20 +/- 1-kDa RESP18 protein is cleaved to an 18 +/- 1-kDa protein and sequestered within the lumen of the rough endoplasmic reticulum. Tissue in situ hybridization analysi s shows that RESP18 mRNA is highly expressed in both the intermediate and anterior pituitary, as well as in the paraventricular and supraopt ic nuclei of the hypothalamus.