Monensin influences basal and human growth hormone-releasing hormone 44-induced release of stored and new rat growth hormone and prolactin

When previous data suggested a growth hormone-releasing factor (GRF)-sensitive branch in intracellular hormone processing, the monensin-sensitive Golgi apparatus seemed a likely candidate. We examined monensin's effect on basal and GRF-stimulated release of newly synthesized and stored rat growth hormone (rGH) and rat prolactin (rPRL). ¹⁴C-Pre-labeled, perifused rat pituitary fragments were exposed to [³H]leucine in 0-10 fiM monensin; a pulse of 3 nM GRF assessed subsequent secretory responsivity. Monensin dose-dependently reduced basal release of stored [¹⁴C]rGH and [¹⁴C]rPRL. GRF timulated release of stored [¹⁴C]hormone was doubled after 0.03 μM and 0.1 μM monensin; higher concentrations diminished stored hormone release. Low concentrations of monensin accelerated basal (0.03 μM and 0.1 μM) and GRF-stimulated (0.03 μM) [³H]rGH and [³H]rPRL release without altering recovery; higher monensin concentrations (≥1 μM) reduced basal, and abolished GRF-stimulated, new hormone release and reduced total [³H]rGH and [³H]rPRL recovery. These data are consistent with a GRF-sensitive and monensin-influenced branch in intracellular hormone processing that regulates the fraction of new hormone exiting the cell without prior immersion in storage compartments.