Chronic exposure of cultured rat anterior pituitary cells to GRF causes partial loss of responsiveness to GRF.

Pretreatment of primary cultures of rat anterior pituitary cells with 500 pM rhGRF for 24 h resulted in a partial loss of responsiveness to GRF. When pretreated cells were rechallenged with increasing concentrations of rhGRF, maximal GH secretion was significantly lower than control, since prolonged exposure to the peptide resulted in depletion of releasable GH pools: 3.04 +/- 0.39 and 0.63 +/- 0.08 micrograms GH per 0.15 X 10(6) cells in control and treated cells, respectively. Possible desensitization, however, was indicated, since chronic exposure to rhGRF increased the EC50 for GH secretion by 5.5-fold. Pretreatment with 2 mM 8BrcAMP for 24 h also caused significant depletion of cellular GH. Consequently, maximal GH secretory response of these cells was blunted as well. However, in contrast to rhGRF-pretreatment, 8BrcAMP-pretreatment did not significantly affect the EC50 value for GH secretion. As another index for cellular responsiveness, cAMP production was also monitored. After a 24-h incubation with 500 pM rhGRF, attenuation of adenylate cyclase activity was evident, since the EC50 value for cAMP production was 2.8-fold greater than control. These results suggest that prolonged pretreatment with GRF results in a partial loss of responsiveness to GRF and this may be explained by desensitization and to some extent by depletion of GH stores.