POSTSOMATOSTATIN HYPERSECRETION OF GROWTH-HORMONE FROM PERIFUSED RAT ANTERIOR-PITUITARY-CELLS IS DEPENDENT ON CALCIUM INFLUX

The role of ionic calcium (Ca2+) in the rebound secretion of growth ho rmone (GH) following termination of somatostatin (SRIF) administration was investigated in vitro by perifusion of acutely dispersed rat ante rior pituitary cells. Treatment with 10 nM SRIF for 40 min significant ly reduced the mean GH secretory rate by 3.3 +/- 0.2 ng min-1 represen ting a 58% decrease from baseline (p < 0.01). Following the withdrawal of SRIF treatment, GH levels surged 3- to 5-fold relative to baseline with the mean secretion rate increasing by 4.5 +/- 0.99 ng min-1 (p < 0.05). GH rebound secretion following SRIF removal from the perifusio n medium was completely abolished (p < 0.01) when zero calcium medium (0 Ca2+) or medium containing 2 mM cobalt chloride (Co2+) were adminis tered after SRIF termination. Perifusion with 0 Ca2+ caused the GH rel ease rate to return to above baseline levels. In contrast, Co2+ perifu sion caused the GH secretion rate to remain at the level observed duri ng SRIF treatment (-4.52 +/- 0.38 ng min-1 relative to baseline; p < 0 .01). Similarly, when cells were exposed to Co2+ alone, a reduction in the rate of GH secretion (-3.96 +/- 0.56 ng min-1; p < 0.0 1) was evi dent. After termination of Co2+ treatment, either by itself or followi ng SRIF pretreatment, and upon changing from 0 Ca2+ to normal calcium- containing medium following SRIF pretreatment, a significant overshoot in GH release similar to SRIF withdrawal-induced GH release was obser ved (p < 0.05 and 0.0 1, respectively). Given that these agents interf ere with the normal flux of calcium from the extracellular space, our data demonstrate that the rebound secretion of GH following SRIF withd rawal is dependent on Ca2+ influx. Co2+ and SRIF both lower intracellu lar Ca2+ concentration and cause membrane hyperpolarization through th e enhancement of potassium efflux. Voltage-sensitive Ca2+ channels in the extracellular membrane tend to remain closed with the reduction of membrane potential, lowering intracellular Ca2+ concentration and pre venting GH release. Following termination of treatment with hyperpolar izing agents, membrane repolarization ensues, allowing voltage-depende nt activation of Ca2+ influx and release of accumulated hormone stored in vesicles. In vivo, a diminution of SRIF dominance at the pituitary may function as a molecular switch permitting GH release, resulting i n a large secretory episode amplified in the presence of GH-releasing hormone.