Somatostatin Inhibition of Growth Hormone Release in Goldfish: Possible Targets of Intracellular Mechanisms of Action

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Previous studies have demonstrated that growth hormone (GH) release in goldfish is under the stimulatory control of gonadotropin-releasing hormone (GnRH) and dopamine and the inhibitory control of somatostatin (SRIF). GnRH stimulation is mediated through protein kinase C (PKC)- and calcium-dependent mechanisms, whereas dopamine D1 receptor activation increases GH secretion through cyclic (c) AMP-dependent intracellular signal transduction pathways. In this study, the mechanisms of SRIF inhibition on GH secretion were examined using primary cultures of dispersed goldfish pituitary cells in static incubation. Application of 1 μMSRIF inhibited the GH-release responses to 100 nMsalmon GnRH, 100 nMchicken GnRH-II, and 1 μMSKF38393, a D1 agonist. These results 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 μMdioctanoyl glycerol and 100 nMtetradecanoyl phorbol acetate) and to two ionophores (10 μMA23187 and 10 μMionomycin). Similarly, SRIF abolished the GH responses to an activator of adenylate cyclase (10 μMforskolin), a membrane-permeant cAMP analog (1 mM8-bromo-cAMP), and a voltage-sensitive calcium channel agonist (1 μMBay K 8644). Taken together, these observations indicate that the inhibitory actions of SRIF on D1- and GnRH-stimulated GH release can be exerted at sites distal to cAMP production and PKC activation, respectively. SRIF also exerts its effect at sites distal to calcium mobilization. Since SRIF inhibition was more effective against Bay K 8644-induced response than against ionophore-induced GH response, an inhibitory action at the level of extracellular calcium entry through voltage-sensitive channels is also possible.