Growth and differentiation of pancreatic acinar cells: independent effects of glucocorticoids on AR42J cells.
Dexamethasone (DEX) inhibits growth and induces differentiation in rat pancreatic acinar AR42J cells. We wished to determine whether growth and differentiation are mutually exclusive in AR42J cells and whether DEX effects on growth and differentiation are mutually dependent or independent. Inhibition of DNA synthesis, assessed by [3H]thymidine incorporation, was detectable after 6 h, half-maximal after 12 h, and complete after 18-h DEX treatment, at which time incorporation was reduced to 9.0% of control. The half-maximal effective dose for inhibition of DNA synthesis was 0.5 nM, and maximal inhibition was achieved with 10 nM DEX. This dose-response was similar to that previously reported for DEX-induced parameters of differentiation. The rank order of potency for inhibition of DNA synthesis by various steroid hormones was DEX greater than corticosterone greater than aldosterone greater than progesterone. Hydroxyurea or serum starvation inhibited growth to the same extent as DEX but did not induce differentiation. Moreover, hydroxyurea or serum starvation did not block the ability of DEX to induce differentiation. Addition of either EGF or insulin significantly reversed the growth inhibitory effects of submaximal (1 nM) DEX. In cultures released from growth inhibition, 1 nM DEX increased cellular amylase content 5.9- to 6.5-fold, similar to the amylase increase in growth-inhibited cultures. Therefore, growth inhibition and differentiation are independent delayed events regulated by DEX in AR42J cells.
Guthrie
J
J
Department of Physiology, University of Michigan, Ann Arbor 48109.
Williams
J A
JA
Logsdon
C D
CD
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000450:Aldosterone / Q000494:pharmacology; D000681:Amylases / Q000032:analysis / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D006918:Hydroxyurea / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D010179:Pancreas / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D000305:Adrenal Cortex Hormones; D005938:Glucocorticoids; D007328:Insulin; D014316:Tritium; D000450:Aldosterone; D011374:Progesterone; D004815:Epidermal Growth Factor; D003907:Dexamethasone; D004247:DNA; D000681:Amylases; D013936:Thymidine; D006918:Hydroxyurea