Inhibitory Actions of Somatostatin, Dexamethasone and Oleic Acid on Growth Hormone (GH) Release and Cytosolic Ca<sup>2+</sup> Concentration Induced by GH-Releasing Peptide-I (GHRP-1) in Ovine Anterior Pituitary Cells

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  • ヒツジ下垂体前葉細胞における成長ホルモン放出ペプチド(GHRP-1)刺激時のGH放出と細胞内カルシウム濃度に及ぼすソマトスタチン,デキサメサゾンおよびオレイン酸の抑制効果
  • Inhibitory Actions of Somatostatin Dexa

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We investigated the effect of a second generation GHRP (CHRP-1: Ala-His-D β NalAla-Trp-DPhe-Lys-NH2) on GH release and intracellular calcium concentration ([Ca2+]i) to define the signal transduction mechanisms involved in the action and in reference to the inhibitory effects of some inhibitors for GH release such as somatostatin (SRIF), dexamethasone (DEX) and oleic acid (OA) in primary cultured ovine anterior pituitary (AP) cells. GHRP-1 caused an increase in GH release in a concentratio-depende manner (P<0.05), and the maximum response was gained at 10μM. GH response induced by 10μM GHRP was significantly (P<0.05) decreased by simultaneous incubation with SRIF (100nM), DEX (100nM), or OA (100μM) to 46±5, 59±7 and 65±8% (mean±SE) of the control value, respectively. The basal [Ca2+]i was 161±5nM and GHRP-I increased [Ca2+]i in a concentration-dependent manner(P<0.001). The maximal increment in [Ca2+]i induced by 10μM GHRP-1 was 37±3nM, which was significantly reduced and changed to a transient response when Ca2+ influx was blocked with an L-type Ca2+ channel antagonist nifedipine (lμM) or by removal of medium calcium with an excess EGTA (1.4mM). The values of [Ca2+]i at the peak and at lmin after GHRP-1 addition were significantly reduced (P<0.05) in the medium containing either SRIF, DEX or OA. Namely, SRIF (100nM) significantly (P<0.05) lowered the resting [Ca2+]i with less marked effect on the GHRP-1-stimulated rise in [Ca2+]i, whereas DEX (100nM) and OA (100μM) reduced the 10μM GKRP-stimulated rise in [Ca2+]i without affecting basal [Ca2+]i. From these results, we conclude that: 1) the mechanism by which GHRP-1 raises [Ca2+]i and results in GH release involves the infiux of extracellular Ca2+; and 2) SRIF, DEX and OA may inhibit GHRP-1-induced GH release by mechanisms that partly depend on [Ca2+]i in ovine AP cells.

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