title: Transforming growth factor-beta (TGF-beta 1) inhibits pancreatic acinar cell growth.
abstract: Effects of transforming growth factor (TGF)-beta 1 on mouse pancreatic acinar cell growth and rapid intracellular responses to cholecystokinin (CCK) were examined in vitro. TGF-beta 1 inhibited [3H]thymidine incorporation stimulated by either the CCK analogue caerulein, epidermal growth factor, or insulin. TGF-beta 1 inhibition of growth stimulated by a maximal dose of caerulein (1 nM) was dose dependent with one-half maximal effects occurring at approximately 5 pM and maximal inhibition seen with 30 pM. In contrast to its effects on CCK-stimulated [3H]thymidine incorporation, TGF-beta 1 had no effect on CCK-stimulated increases in amylase release or intracellular Ca2+ concentration. To determine whether TGF-beta 1 might be an autocrine growth regulator, pancreatic mRNA was probed for the presence of TGF-beta 1 transcripts. TGF-beta 1 mRNA was not detected in whole pancreas but was detectable with increasing abundance over time in primary cultures of pancreatic acinar cells. The appearance of the TGF-beta 1 mRNA corresponded to the period of rapid cellular proliferation in vitro. These results suggest that TGF-beta 1 may be an autocrine growth inhibitor in the pancreas and that the inhibitory effects of TGF-beta 1 on pancreatic acinar cell growth occur at sites distal to those involved in stimulus-secretion coupling.
authors.affiliation: Department of Physiology, University of Michigan, Ann Arbor 48109.
authors.forename: C D
authors.initials: CD
authors.lastname: Logsdon
authors.forename: L
authors.initials: L
authors.lastname: Keyes
authors.forename: R D
authors.initials: RD
authors.lastname: Beauchamp
mesh_terms: D000818:Animals; D002455:Cell Division; D002766:Cholecystokinin / Q000494:pharmacology; D010179:Pancreas / Q000166:cytology* / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000494:pharmacology*
chemical_list: D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D002766:Cholecystokinin