Interaction of somatostatin inhibition and dibutyryl cyclic AMP or potassium stimulation of growth hormone release from perifused rat pituitaries

The functional interrelation of somatostatin (SRIF), dibutyryl cyclic AMP (DBcAMP), and potassium in the release of stored rat growth hormone (rGH) from pituitary explants was studied. The stored hormone pool was identified by prelabeling with [³H ]leucine, and hormone release was followed in an in vitro perifusion system by specific immunoprecipitation. Pulses of 10⁻³M DBcAMP or 21 mM potassium produced pulses of stored [³H]rGH release in the presence (blunted) or absence of maximal (25 nM) SRIF inhibition. In the absence of SRIF, continuous potassium also caused only a pulse of [³H]rGH release whereas continuous DBcAMP produced both an early pulse and a late sustained increased release of [³H]rGH. SRIF blocked DBcAMP-stimulated [³H ]rGH release, but not its stimulated accumulation in an immediately releasable pool which was then discharged when SRIF inhibition was removed. Potassium did not stimulate the accumulation of [³H ]rGH behind the SRIF block in the immediately releasable pool. A model of intracellular rGH storage and release integrating these observations is presented. It: is proposed that one of SRIF’s functions may be to block temporarily hormone release from the somatotroph, while not blocking hormone accumulation in a releasable form. Withdrawal of the SRIF block might at that point permit discharge of this releasable rGH.