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Growth Hormone and Prolactin Stimulate the Expression of Rat Preadipocyte Factor-1/-Like Protein in Pancreatic Islets: Molecular Cloning and Expression Pattern during Development and Growth of the Endocrine Pancreas¹

Hagedorn Research Institute, Gentofte (C.C., K.L., P.G., N.B., B.M., J.H.N.), and the Department of Molecular Cell Biology, Statens Seruminstitut (D.I., L.-I.L.), Copenhagen, Denmark

Address all correspondence and requests for reprints to: Dr. Carina Carlsson (nee Svensson), Department of Medical Cell Biology, Box 571, Biomedical Center, Uppsala University, 751 23 Uppsala, Sweden. E-mail Carina.Carlsson{at}medcellbiol.uu.se

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 -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 ß-cells.

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