Yamashita S, Melmed S
Endocrinology. 1986 Jan;118(1):176-82. doi: 10.1210/endo-118-1-176.
Somatomedin preparations have previously been shown to suppress GH release. The effects of a synthetic recombinant human insulin-like growth factor analog (IGF-I; Thr 59) were, therefore, tested on long term GH secretion by male rat pituitary monolayer cell cultures grown in serum-free defined medium. IGF-I (3.25 nM) maximally suppressed basal GH secretion for up to 72 h by 66%, with an ED50 of 0.1 nM. Human pancreatic GRF-(1-44) (GHRH; 1 nM) stimulated GH secretion by 230% during 72 h. IGF-I (0.13 nM) suppressed GHRH-stimulated GH secretion by 30% (P less than 0.005). IGF-I (0.625 nM) completely abolished stimulation of GH by GHRH (1 nM), while higher doses of IGF-I (up to 6.5 nM) actually suppressed GH secretion even in the presence of GHRH (up to 1 nM). The depletion of intracellular GH levels in GHRH-treated cells was reversed by IGF-I (3.25 nM). PRL secretion was not altered in the same cells by IGF-I. Equivalent doses of epidermal growth factor and fibroblast growth factor did not alter basal or GHRH-stimulated GH secretion. Nitrocellulose dot hybridization of immobilized pituitary cell RNA extracts with rat GH [32P]cDNA showed that cellular GH mRNA levels were lowered in IGF-I-treated cells in a dose-dependent manner. Maximal suppression of GH mRNA was achieved with 0.65 nM IGF-I. IGF-I also inhibited the 3-fold stimulation of GH mRNA induced by 1 nM GHRH. The data show that IGF-I directly modulates GH gene expression at the level of the somatotroph by inhibiting basal and GHRH-stimulated GH secretion and GH mRNA levels during 72 h. These effects may occur at different postranscriptional sites. Alternatively, they may result from a direct inhibition of IGF-I on GH gene transcription.
生长调节素制剂此前已被证明可抑制生长激素（GH）的释放。因此，在无血清限定培养基中培养的雄性大鼠垂体单层细胞培养物上，测试了一种合成重组人胰岛素样生长因子类似物（IGF-I；苏氨酸59）对长期GH分泌的影响。IGF-I（3.25 nM）在长达72小时内最大程度地抑制基础GH分泌达66%，半数有效剂量（ED50）为0.1 nM。人胰腺生长激素释放因子（GRF）-(1 - 44)（GHRH；1 nM）在72小时内刺激GH分泌增加230%。IGF-I（0.13 nM）抑制GHRH刺激的GH分泌达30%（P < 0.005）。IGF-I（0.625 nM）完全消除了GHRH（1 nM）对GH的刺激，而更高剂量的IGF-I（高达6.5 nM）实际上即使在存在GHRH（高达1 nM）的情况下也抑制GH分泌。IGF-I（3.25 nM）可逆转GHRH处理细胞中细胞内GH水平的消耗。IGF-I对相同细胞中的催乳素（PRL）分泌没有影响。等量的表皮生长因子和成纤维细胞生长因子不会改变基础或GHRH刺激的GH分泌。用大鼠GH [32P] cDNA对固定化垂体细胞RNA提取物进行硝酸纤维素斑点杂交显示，IGF-I处理的细胞中细胞GH mRNA水平以剂量依赖方式降低。用0.65 nM IGF-I可实现对GH mRNA的最大抑制。IGF-I还抑制了1 nM GHRH诱导的GH mRNA 3倍的刺激。数据表明，IGF-I在72小时内通过抑制基础和GHRH刺激的GH分泌以及GH mRNA水平，直接在生长激素细胞水平调节GH基因表达。这些作用可能发生在不同的转录后位点。或者，它们可能是由于IGF-I对GH基因转录的直接抑制所致。
