Hormonal regulation of initiation of DNA synthesis and of differentiated function in Y-1 adrenal cortical cells.
ACTH, 8-Br-cAMP, and serum deprivation arrested Y-1 functional mouse adrenal tumor cells in the G1 phase of the cell cycle. Though ACTH and 8-Br-cAMP treated cells were larger with increased macromolecular synthetic rates compared to cells arrested in G1 by serum removal, a similar 8- to 10-hours lag to initiation of DNA synthesis was observed after either ACTH or 8-Br-cAMP removal or after serum addition. After the 8- to 10-hour lag period, cells entered S phase exponentially. ACTH or 8-Br-cAMP opposed serum induced DNA synthesis initiation only when added prior to S. Once commitment to DNA synthesis occurred, ACTH or 8-Br-cAMP addition did not inhibit DNA synthesis although 8-Br-cAMP induced a secondary block in G2. Though ACTH and 8-Br-cAMP inhibited serum induced initiation of DNA synthesis and did not affect serum induced cellular hypertrophy, both substances increased the steroidogenic capacity of the cell. ACTH and 8-Br-cAMP thus appear to specifically oppose the stimulatory effects of serum on initiation of DNA synthesis while inducing the differentiated function of the cell.
D004092:20-alpha-Dihydroprogesterone / Q000096:biosynthesis*; D000306:Adrenal Cortex Neoplasms; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D001769:Blood; D001966:Bromine; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured / Q000187:drug effects* / Q000378:metabolism; D003470:Culture Media; D000242:Cyclic AMP / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D006908:Hydroxyprogesterones / Q000096:biosynthesis*; D006918:Hydroxyurea / Q000494:pharmacology; D051379:Mice; D011374:Progesterone / Q000031:analogs & derivatives*; D013806:Theophylline / Q000494:pharmacology
D003470:Culture Media; D004273:DNA, Neoplasm; D006908:Hydroxyprogesterones; D004092:20-alpha-Dihydroprogesterone; D011374:Progesterone; D000324:Adrenocorticotropic Hormone; D013806:Theophylline; D000242:Cyclic AMP; D001966:Bromine; D006918:Hydroxyurea