Hormonal regulation of initiation of DNA synthesis and of differentiated function in Y-1 adrenal cortical cells

Abstract

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‐hour 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.