title: Growth hormone and prolactin stimulate the expression of rat preadipocyte factor-1/delta-like protein in pancreatic islets: molecular cloning and expression pattern during development and growth of the endocrine pancreas.
abstract: GH and PRL have been shown to stimulate proliferation and insulin production in islets of Langerhans. To identify genes regulated by GH/PRL in islets, we performed differential screening of a complementary DNA library from neonatal rat islets cultured for 24 h with human GH (hGH). One hGH-induced clone had 96% identity with mouse preadipocyte factor-1 (Pref-1, or delta-like protein (Dlk)]. The size of Pref-1 messenger RNA (mRNA) in islets was 1.6 kilobases, with two less abundant mRNAs of 3.7 and 6.2 kilobases. The Pref-1 mRNA content of islets from adult rats was only 1% of that in neonatal islets. Pref-1 mRNA was markedly up-regulated in islets from pregnant rats from day 12 to term compared with those from age-matched female rats. Two peaks in mRNA expression were observed during gestation, one on day 14 and the other at term, whereafter it decreased to nonpregnant levels. Pref-1 mRNA was up-regulated 3- to 4-fold in neonatal rat islets of Langerhans after 48-h culture with hGH, as found also with bovine GH or ovine PRL. During the development of pancreas from embryonic day 12 (E12) to postnatal day 4, we observed a 2-fold increase in Pref-1 mRNA on E17 and a 5-fold increase at birth, followed by a rapid decline on postnatal day 4. Pref-1 immunoreactivity was found in a subpopulation of insulin cells of neonatal islets of Langerhans. At an early embryonal stage (E13), most cells of the pancreatic anlage were Pref-1 positive, becoming predominantly restricted to the insulin-producing cells during development. In conclusion, these findings suggest that Pref-1 is involved in both differentiation and growth of beta-cells.
authors.affiliation: Hagedorn Research Institute, Gentofte, Denmark. Carina.Carlsson@medcellbiol.uu.se
authors.forename: C
authors.initials: C
authors.lastname: Carlsson
authors.forename: D
authors.initials: D
authors.lastname: Tornehave
authors.forename: K
authors.initials: K
authors.lastname: Lindberg
authors.forename: P
authors.initials: P
authors.lastname: Galante
authors.forename: N
authors.initials: N
authors.lastname: Billestrup
authors.forename: B
authors.initials: B
authors.lastname: Michelsen
authors.forename: L I
authors.initials: LI
authors.lastname: Larsson
authors.forename: J H
authors.initials: JH
authors.lastname: Nielsen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D002135:Calcium-Binding Proteins; D003001:Cloning, Molecular; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D013006:Growth Hormone / Q000494:pharmacology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007515:Islets of Langerhans / Q000254:growth & development* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011388:Prolactin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012097:Repressor Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment
chemical_list: D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; C512925:Dlk1 protein, mouse; C512923:Dlk1 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D011388:Prolactin; D013006:Growth Hormone