title: RESP18, a novel endocrine secretory protein transcript, and four other transcripts are regulated in parallel with pro-opiomelanocortin in melanotropes.
abstract: The homogeneous nature of the rat intermediate pituitary makes it a powerful model system in which to study peptide hormone secretion. Adult male rats were treated with bromocriptine, a dopamine agonist, or haloperidol, a dopamine antagonist, for 3 weeks. In cDNA libraries prepared from the neurointermediate pituitaries of these rats, pro-opiomelanocortin (POMC) expression exhibited the expected decrease in response to bromocriptine, and increase in response to haloperidol. We report the 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 carboxy-peptidase E, chromogranin B, binding protein/glucose-regulated protein, and tenascin, two novel regulated transcripts are described. The expression of one of these novel transcripts, RESP18, is limited to neural and endocrine tissue. The RESP18 transcript is approximately 800 nucleotides in length; its cognate translation product is 20 +/- 1 kDa, contains a putative signal sequence, and has many characteristics of a secreted protein. Cell-free translation experiments in the presence of microsomal 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 analysis shows that RESP18 mRNA is highly expressed in both the intermediate and anterior pituitary, as well as in the paraventricular and supraoptic nuclei of the hypothalamus.
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: B T
authors.initials: BT
authors.lastname: Bloomquist
authors.forename: D N
authors.initials: DN
authors.lastname: Darlington
authors.forename: R E
authors.initials: RE
authors.lastname: Mains
authors.forename: B A
authors.initials: BA
authors.lastname: Eipper
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001971:Bromocriptine / Q000494:pharmacology; D005786:Gene Expression Regulation; D015723:Gene Library; D005796:Genes; D006220:Haloperidol / Q000494:pharmacology; D007031:Hypothalamus / Q000378:metabolism; D017403:In Situ Hybridization; D008297:Male; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D010902:Pituitary Gland / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D014018:Tissue Distribution
chemical_list: D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C086381:regulated endocrine secretory protein 18; D001971:Bromocriptine; D011333:Pro-Opiomelanocortin; D006220:Haloperidol