Evidence that diminished pituitary responsivity to GHRF is secondary to intracellular GH pool depletion

In a perifused dispersed rat anterior pituitary cell system, growth hormone (GH) secretion became attenuated in response to repeated pulsatile or prolonged exposure to submaximal stimulatory concentrations of rat growth hormone-releasing factor (GHRF). However, persistent intracellular GH stores could be released upon subsequent challenge with the membrane depolarizing agent KCl, forskolin, or the phorbol ester, tetradecanoylphorbol acetate (TPA). The GH secretory response to repeated pulsatile administration of either KCl or forskolin also became attenuated. In these experiments, persistent intracellular GH stores could be released upon subsequent GHRF stimulation. Repeated challenge with pulses of TPA failed to elicit any GH release after the initial stimulatory response, although a subsequent GHRF pulse was stimulatory, indicating persistence of intracellular GH stores. These data are compatible with the hypothesis that the decreased GH secretory responsivity to GHRF, which was observed in the course of these experiments, is caused by the functional depletion of specific secretagogue-sensitive pools of intracellular GH, rather than by receptor-mediated desensitization.