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/

GH and PRL have been shown to stimulate proliferation and insulin prod uction 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 facto r-1 (Pref-1, or delta-like protein (Dlk)]. The size of Pref-1 messenge r 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 adul t rats was only 1% of that in neonatal islets. Pref-1 mRNA was markedl y up-regulated in islets from pregnant rats from day 12 to term compar ed with those from age-matched female rats. Two peaks in mRNA expressi on were observed during gestation, one on day 14 and the other at term , whereafter it decreased to nonpregnant levels. Pref-1 mRNA was up-re gulated 3- to 4-fold in neonatal rat islets of Langerhans after 48-h c ulture 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 in crease at birth, followed by a rapid decline on postnatal day 4. Pref- 1 immunoreactivity was found in a subpopulation of insulin cells of ne onatal islets of Langerhans. At an early embryonal stage (E13), most c ells of the pancreatic anlage were Pref-1 positive, becoming predomina ntly restricted to the insulin-producing cells during development. In conclusion, these findings suggest that Pref-1 is involved in both dif ferentiation and growth of beta-cells.