SOMATOSTATIN INHIBITION OF GROWTH-HORMONE RELEASE IN GOLDFISH - POSSIBLE TARGETS OF INTRACELLULAR MECHANISMS OF ACTION

Previous studies have demonstrated that growth hormone (GH) release in goldfish is under the stimulatory control of gonadotropin-releasing h ormone (GnRH) and dopamine and the inhibitory control of somatostatin (SRIF). GnRH stimulation is mediated through protein kinase C (PKC)- a nd calcium-dependent mechanisms, whereas dopamine D1 receptor activati on increases GH secretion through cyclic (c) AMP-dependent intracellul ar signal transduction pathways. In this study, the mechanisms of SRIF inhibition on GH secretion were examined using primary cultures of di spersed goldfish pituitary cells in static incubation. Application of 1 mu M SRIF inhibited the GH-release responses to 100 nh salmon GnRH, 100 nM chicken GnRH-II, and 1 mu M SKF38393, a D1 agonist. These resul ts indicate that inhibitory action of SRIF on stimulated GH release is direct, at the level of the pituitary cells. Addition of SRIF reduced the GH release responses to two activators of PKC (100 mu M dioctanoy l glycerol and 100 nM tetradecanoyl phorbol acetate) and to two ionoph ores (10 mu M A23187 and 10 mu M ionomycin). Similarly SRIF abolished the GH responses to an activator of adenylate cyclase (10 mu M forskol in), a membrane-permeant cAMP analog (1 mM 8-bromo-cAMP), and a voltag e-sensitive calcium channel agonist (1 mu M Bay K 8644). Taken togethe r, these observations indicate that the inhibitory actions of SRIF on D1- and GnRH-stimulated GH release can be exerted at sites distal to c AMP production and PKC activation, respectively SRIF also exerts its e ffect at sites distal to calcium mobilization. Since SRIF inhibition w as more effective against Bay K 8644-induced response than against ion ophore-induced GH response, an inhibitory action at the level of extra cellular calcium entry through voltage-sensitive channels is also poss ible. (C) 1997 Academic Press.