Lamberts S W, den Holder F, Hofland L J
Department of Medicine, Erasmus University, Rotterdam, The Netherlands.
Endocrinology. 1989 Feb;124(2):905-11. doi: 10.1210/endo-124-2-905.
Both insulin-like growth factor I (IGF-I) and somatostatin (SRIH) have been shown to directly inhibit GH release and the total GH content of cultured pituitary cells. In the present study we evaluated the interrelationship between the effects of a recombinant human IGF-I analog ([Thr59]IGF-I) and SRIH on GH release by cultured normal rat pituitary cells together with the effects of glucocorticoids. In all experiments anterior pituitary cells were preincubated for 24 h without or with IGF-I, SRIH, and/or dexamethasone. Thereafter, 24-h incubations without or with IGF-I, dexamethasone, SRIH, and GHRH were performed. Both IGF-I and SRIH inhibited basal and GHRH-stimulated GH release in a dose-dependent manner; the maximal inhibitory concentrations were 5 nM IGF-I and 10 nM SRIH. These concentrations inhibited basal and GHRH-stimulated GH release by 23% and 40% (IGF-I) and 80% and 85% (SRIH), respectively. The combination of IGF-I and low concentrations of SRIH exerted an additive inhibitory effect on GHRH-stimulated GH release; IGF-I (1 nM) and SRIH (10 pM) together inhibited GH release by 50%, while the maximal inhibitory concentrations of 5 nM IGF-I and 10 nM SRIH virtually completely inhibited GH release (by 93%). Preincubation with 5 and 100 nM dexamethasone attenuated the sensitivity of somatotrophs to SRIH and completely abolished the inhibitory effects of IGF-I. This effect of dexamethasone could be reversed by coincubation with the glucocorticoid receptor antagonist RU 38486. High concentrations of 5-10 nM of the recombinant human IGF-I analog stimulated PRL cell content (5 and 10 nM) and release (10 nM), while a purified IGF-I preparation extracted from human blood exerted a parallel inhibitory effect on GH and PRL release. We conclude that 1) IGF-I and SRIH exert an additive direct inhibitory effect on basal and GHRH-stimulated GH secretion by normal cultured pituitary cells; 2) glucocorticoids directly attenuate the sensitivity of somatotrophs to SRIH, but completely prevent the inhibitory effects of IGF-I on GH secretion; and 3) in contrast to a purified IGF-I preparation extracted from human blood (which inhibits GH and PRL release) high concentrations of the recombinant IGF-I preparation (which inhibit GH release) stimulate PRL production.
胰岛素样生长因子I（IGF-I）和生长抑素（SRIH）均已被证明可直接抑制生长激素（GH）的释放以及培养的垂体细胞中的总GH含量。在本研究中，我们评估了重组人IGF-I类似物（[Thr59]IGF-I）和SRIH对培养的正常大鼠垂体细胞GH释放的影响之间的相互关系，以及糖皮质激素的影响。在所有实验中，垂体前叶细胞在无或有IGF-I、SRIH和/或地塞米松的情况下预孵育24小时。此后，在无或有IGF-I、地塞米松、SRIH和生长激素释放激素（GHRH）的情况下进行24小时孵育。IGF-I和SRIH均以剂量依赖性方式抑制基础和GHRH刺激的GH释放；最大抑制浓度分别为5 nM IGF-I和10 nM SRIH。这些浓度分别抑制基础和GHRH刺激的GH释放23%和40%（IGF-I）以及80%和85%（SRIH）。IGF-I和低浓度SRIH的组合对GHRH刺激的GH释放产生相加抑制作用；IGF-I（1 nM）和SRIH（10 pM）共同抑制GH释放50%，而5 nM IGF-I和10 nM SRIH的最大抑制浓度几乎完全抑制GH释放（93%）。用5和100 nM地塞米松预孵育可减弱生长激素细胞对SRIH的敏感性，并完全消除IGF-I的抑制作用。地塞米松的这种作用可通过与糖皮质激素受体拮抗剂RU 38486共同孵育而逆转。高浓度5 - 10 nM的重组人IGF-I类似物刺激催乳素（PRL）细胞含量（5和10 nM）和释放（10 nM），而从人血中提取的纯化IGF-I制剂对GH和PRL释放产生平行抑制作用。我们得出结论：1）IGF-I和SRIH对正常培养的垂体细胞的基础和GHRH刺激的GH分泌产生相加直接抑制作用；2）糖皮质激素直接减弱生长激素细胞对SRIH的敏感性，但完全阻止IGF-I对GH分泌的抑制作用；3）与从人血中提取的纯化IGF-I制剂（抑制GH和PRL释放）相反，高浓度的重组IGF-I制剂（抑制GH释放）刺激PRL产生。
