Physiological concentrations of atrial natriuretic factors with intact N-terminal sequences inhibit corticotropin-releasing factor-stimulated adrenocorticotropin secretion from cultured anterior pituitary cells.

The effectiveness of atrial natriuretic factors (ANFs) as inhibitors of CRF-stimulated ACTH secretion was examined in cultured rat anterior pituitary cells. alpha ANF-(1-28) significantly inhibited ACTH release stimulated by 1-5 nM CRF. At the most effective concentration of 100 pM, alpha ANF-(1-28) inhibited ACTH release by 40.1% (P less than 0.001). This effect was manifested after 3 h, but not after 0.5 or 1 h, of incubation, suggesting that ACTH synthesis may have been reduced. Conversely, alpha ANF-(5-28), at concentrations of 10 pM to 10 nM, had no effect on ACTH secretion after 0.5, 1, or 3 h. alpha ANF-(1-11) weakly inhibited ACTH secretion at concentrations of 100 and 1000 pM. Again, these effects were observed after 3 h, but not after 0.5 or 1 h, of incubation. These results suggest that ANF-induced inhibition of CRF-stimulated ACTH release requires 1) an intact N-terminal sequence of the ANF peptide, 2) low concentrations, and 3) more than 1 h of incubation. The results explain previous negative evidence and suggest that alpha ANF-(1-28) may be a physiological inhibitor of ACTH secretion.