Effects of ACTH and ACTH fragments on DNA synthesis in guinea-pig adrenal segments kept in organ culture

Stimulation of adrenal DNA synthesis by ACTH and its fragments ACTH (Synacthen) and ACTH was investigated. Synthesis of DNA was measured as the increase in the percentage of cells in S-phase (Feulgen densitometry) in guinea-pig adrenal explants kept in organ culture and exposed to the peptides for 5 h at 37 degrees C. ACTH and its C-terminal fragment ACTH (corticotrophin-like intermediate lobe peptide) were found to be potent stimulators of in-vitro adrenal DNA synthesis. The dose-response kinetics were biphasic and optimal responsiveness was reached in both instances at 1 fmol/1-10 pmol/1 (this biological effect of ACTH has hitherto not been described). The N-terminal fragment ACTH gave only minimal responses. Thyrotrophin and LH, tested as controls, did not induce adrenal DNA synthesis. Epidermal growth factor was a potent stimulator of adrenal DNA synthesis in vitro. Our data suggest a trophic action of the C-terminal part of the corticotrophic molecule. Clear trophic effects were also found for the N-terminal part of the pro-opiomelanocortin molecule N-POC (optimum 0.1 nmol/l) and N-POC(51-62) (optimum 0.1 pmol/l). The latter observations support earlier concepts that this part of the pro-opiomelanocortin molecule has a stimulatory effect on adrenal DNA synthesis.