title: Effects of ACTH and ACTH fragments on DNA synthesis in guinea-pig adrenal segments kept in organ culture.
abstract: 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.
authors.affiliation: Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: N M
authors.initials: NM
authors.lastname: Wulffraat
authors.forename: H A
authors.initials: HA
authors.lastname: Drexhage
authors.forename: P
authors.initials: P
authors.lastname: Jeucken
authors.forename: R D
authors.initials: RD
authors.lastname: van der Gaag
authors.forename: W M
authors.initials: WM
authors.lastname: Wiersinga
mesh_terms: D000302:Adrenal Cortex / Q000187:drug effects* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D006133:Growth Substances / Q000494:pharmacology; D006168:Guinea Pigs; D007986:Luteinizing Hormone / Q000494:pharmacology; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000494:pharmacology*; D011333:Pro-Opiomelanocortin / Q000494:pharmacology; D013972:Thyrotropin / Q000494:pharmacology
chemical_list: D006133:Growth Substances; D010446:Peptide Fragments; D004815:Epidermal Growth Factor; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D007986:Luteinizing Hormone; D013972:Thyrotropin; D004247:DNA