NORMAL AND DISTURBED MOTILITY OF GALLBLADDERANDSPHINCTEROFODDI．

ＮＯＲＭＡＬＡＮＤＤＩＳＴＵＲＢＥＤＭＯＴＩＬＩＴＹＯＦＧＡＬＬＢＬＡＤＤＥＲＡＮＤＳＰＨＩＮＣＴＥＲＯＦＯＤＤＩ．Ａ．Ｊ．Ｐ．Ｍ．Ｓｍｏｕｔ，Ｇ．Ｐ．ｖａｎＢｅｒｇｅ＿Ｈｅｎｅｇｏｕｗｅｎ，ａｎｄＭ．Ｓａｍｓｏｍ．ＤｅｐａｒｔｍｅｎｔｏｆＧａｓｔｒ...     

猪囊尾蚴抗原cC1与γ-干扰素融合蛋白在大肠杆菌中的表达

目的： 构建含猪囊尾蚴抗原ｃ Ｃ１ ｃ Ｄ Ｎ Ａ 与猪γ干扰素（ Ｉ Ｆ Ｎγ） 的融合表达载体。方法： 从已克隆的含人猪囊尾蚴共通抗原ｃ Ｃ１ 的质粒中, 用 Ｐ Ｃ Ｒ 方法扩增出含酶切位点及接头的ｃ Ｃ１ 和 Ｉ Ｆ Ｎγｃ Ｄ Ｎ Ａ, 两ｃ Ｄ Ｎ Ａ 经接头融合后构建成融合形式的原核表达载体转入大肠杆菌 Ｘ Ｌ Ｂｌｕｅ。结果： 经酶切分析, 表明重组载体中含１５ｋｂ 插入片段。 Ｓ Ｄ Ｓ Ｐ Ａ Ｇ Ｅ 显示一５２ ｋ Ｄａ 的诱导产物。结论： 猪 Ｉ Ｆ Ｎγ和猪囊尾蚴抗原ｃ Ｃ１ 融合ｃ Ｄ Ｎ Ａ 在大肠杆菌中获得表达。     

大肠癌EGF受体和增殖细胞核抗原表达的预后意义

目的研究大肠癌表皮生长因子受体（ＥＧＦＲ）和增殖细胞核抗原（ＰＣＮＡ）表达和评价对大肠癌预后的意义。方法应用免疫组化ＬＳＡＢ法检测ＥＧＦＲ和ＰＣＮＡ对有随访资料的大肠癌的表达。结果正常大肠粘膜未发现ＥＧＦＲ阳性表达，而大肠癌有较高表达（７７０％）。ＰＣＮＡ阳性表达中，大肠癌（４６４±２６５％）明显高于正常粘膜（１５１±５４％，Ｐ＜００５）。ＥＧＦＲ表达与大肠癌Ｄｕｋｅｓ分期有关（Ｐ＜００５）。ＰＣＮＡ表达与大肠癌分化程度及Ｄｕｋｅｓ分期有关（Ｐ＜００５）。大肠癌４年生存率ＥＧＦＲ和ＰＣＮＡ表达＞６５％组均明显低于＜２５％组（Ｐ＜００５），ＥＧＦＲ＿ＬＩ和ＰＣＮＡ＿ＬＩ与生存期均有明显负相关。结论ＥＧＦＲ和ＰＣＮＡ表达与大肠癌的进展程度有关，对大肠癌预后的评估有重要价值。     

血清胰岛素样生长因子结合蛋白与肾病大鼠的生长障碍

目的：探讨营养不良、肾病本身的糖皮质激素作为各自独立因素对大鼠血清胰岛素生长因子结合蛋白（ＩＣＦＢＰｓ）浓度的影响，阐明血清ＩＧＦＢＰｓ代谢紊与肾病综合片（ＮＳ）大鼠生长障碍的关系。方法：２４只周龄相同体重相近的雄笥ＳＤ大鼠随机分成正常、食物对照、阿霉素现任地塞米松治疗的阿霉素肾病四组。血清ＩＧＦＢＰＳ浓度和肝脏ＩＧＦＢＰｓｍＲＮＡ表达分别采用Ｗｅｓｔｅｒｎｌｉｇａｎｄｂｌｏｔ和ＲＴ－ＰＣＲ法检测     

γ干扰素对培养的人甲状腺细胞HLA-DR抗原基因表达的影响

ＭＨＣⅡ类抗原ＨＬＡ ＤＲ在致自身免疫性甲状腺病(ＡＩＴＤ)中起着非常重要的作用 ,γ干扰素 (ＩＦＮγ)在调控自身免疫性甲状腺病中的作用日益受到重视 ,同时它对细胞的生长起一定的作用 ,其作用机制未明。本研究运用Ｎｏｒｔｈｅｒｎｂｌｏｔ杂交技术、3 Ｈ ＴｄＲ掺入法及ｃＡＭＰ测定法 ,从细胞学角度分别研究ＩＦＮγ对人甲状腺细胞ＨＬＡ ＤＲ的表达和细胞生长状态的影响 ,以及ＩＦＮγ对细胞ｃＡＭＰ的影响 ,为阐明ＩＦＮγ在Ｇｒａｖｅｓ病中的作用提供理论依据。一、材料与方法1.细胞培养 :(1)标本来源 :Ｇｒａｖｅｓ病甲状腺组…     

大肠癌EGF受体表达对细胞增殖的影响

目的研究ＥＧＦ受体（ＥＧＦＲ）在大肠癌中表达的意义，并探讨其对细胞增殖的影响．方法用免疫组化ＬＳＡＢ法检测８６例大肠癌组织ＥＧＦＲ，ＰＣＮＡ的表达．结果在８６例被检组织中，ＥＧＦＲ阳性表达４４例（５１２％），低分化癌（８００％，４０／５０）、淋巴结转移癌（６８８％，２２／３２）较高分化（３８９％，１４／３６）、淋巴结未受累大肠癌（４０７％，２２／５４）有更高的ＥＧＦＲ表达（Ｐ＜００５）．ＤｕｋｅｓＡ，Ｂ，Ｃ期大肠癌的ＥＧＦＲ表达率分别为３２０％，４８３％，６８８％，Ｃ期与Ａ期比较差异显著；ＥＧＦＲ阳性大肠癌较阴性癌有更高的ＰＣＮＡ标记（两者ＰＣＮＡⅠ，Ⅱ，Ⅲ，Ⅳ级的例数分别为４，８，１７，１５；１４，１６，７，５；Ｐ＜００５）．结论ＥＧＦＲ过表达与大肠癌恶性程度、转移趋势密切相关，并可促使癌细胞过度增生．     

血吸虫病肝纤维化患者转化生长因子β_1mRNA的水平及其临床意义

目的：研究血吸虫病患者 Ｔ Ｇ Ｆβ１ ｍ Ｒ Ｎ Ａ 水平及其临床意义。方法：用 Ｒ Ｔ Ｐ Ｃ Ｒ 加 ｄｏｔｂｌｏｔ法测定血吸虫病患者 Ｐ Ｂ Ｍ Ｃ中 Ｔ Ｇ Ｆβ１ ｍ Ｒ Ｎ Ａ 水平,与肝硬变和肝癌患者作比较,并研究了部分肝脏组织（肝癌患者１６ 例,肝血管瘤患者正常肝组织 ５ 例）中 Ｔ Ｇ Ｆβ１ ｍ Ｒ Ｎ Ａ 水平与 Ｐ Ｂ Ｍ Ｃ中水平的关系。同时,测定血清中 Ｈ Ａ、 Ｌ Ｎ、 ＣｏｌⅠⅤ和 Ｐ ＣⅢ水平,作为衡量肝纤维化活动与否的指标。结果： Ｐ Ｂ Ｍ Ｃ内 Ｔ Ｇ Ｆβ１ ｍ Ｒ Ｎ Ａ 水平在晚期血吸虫病患者组（ｎ＝ ２１,１２６±０１４）,肝硬变患者组（ｎ＝ １５,２０５±０８１）和肝癌患者组（ｎ＝ ２５,１８３±１２９）均显著高于正常对照组（ｎ＝ １６,０６２±０４０）（ Ｐ＜ ００５）。其中晚期血吸虫病患者组又显著低于肝硬变患者组或肝癌患者组（ Ｐ＜ ００５）,后两组差异无显著性（ Ｐ＞ ００５）。肝组织与 Ｐ Ｂ Ｍ Ｃ内 Ｔ Ｇ Ｆβ１ ｍ Ｒ Ｎ Ａ 水平差别无统计学意义（ Ｐ＞ ００５）。血清 Ｈ Ａ、 ＣｏｌⅣ和 Ｌ Ｎ 异常组的 Ｔ Ｇ Ｆβ１ ｍ Ｒ Ｎ Ａ 水平显著高于正常组（ Ｐ＜ ００５）。结论： Ｐ     

胰岛素样生长因子系统的生物活性对低氧性肺血管重建的影响

多种生长因子在低氧性肺血管重建机制中起着重要的作用。但ＩＧＦ－１，ＩＧＦ－１Ｒ和ＩＧＦＢＰｓ的作用，目前尚不十分清楚，肺血管平滑肌细胞，巨噬细胞和肺成纤维细胞均能合成和分泌ＩＧＦ－１。ＩＧＦ－１以自分泌／旁分泌的作用方式刺激血管平滑肌细胞和血管内皮细胞生长；低氧是肺脏ＩＧＤ－１和ＩＧＦ－１ＲｍＲＮＡ表达同时增加，促使肺动脉平滑肌细胞增殖和弹性蛋白合成；但ＩＧＦＢＰｓ在低氧时的变化尚不清楚。故胰岛素     

HORMONAL REGULATION OF GASTRIC EMPTYINGANDITSAPPLICATIONINTHETHERAPYOFGASTROPARESIS．

ＨＯＲＭＯＮＡＬＲＥＧＵＬＡＴＩＯＮＯＦＧＡＳＴＲＩＣＥＭＰＴＹＩＮＧＡＮＤＩＴＳＡＰＰＬＩＣＡＴＩＯＮＩＮＴＨＥＴＨＥＲＡＰＹＯＦＧＡＳＴＲＯＰＡＲＥＳＩＳ．ＴＬ．Ｐｅｅｔｅｒｓ，Ｍ．Ｄ．ＧｕｔＨｏｒｍｏｎｅＬａｂ，Ｌｅｕｖｅｎ，Ｂｅｌｇｉｕｍ．Ｔ...     

恶性疟原FCC-1 HN株EBA-175和HRP-II基因片段在HeLa细胞中的表达及鉴定

目的　在 Ｈｅ Ｌａ 细胞中表达恶性疟原虫红细胞结合蛋白 Ｅ Ｂ Ａ－ １７５ 和富组氨酸蛋白 Ｈ Ｒ Ｐ－ Ｉ Ｉ, 进一步研究其生物学功能和免疫学特性。方法　将 Ｅ Ｂ Ａ－ １７５ 和 Ｈ Ｒ Ｐ－ Ｉ Ｉ 部分基因串接插入 Ｐ Ｃ Ｄ Ｎ Ａ３ 真核表达载体, 获得重组表达质粒 Ｐ Ｃ Ｄ Ｎ Ａ３ Ｅ Ｂ Ａ１７５ － Ｈ Ｒ Ｐ Ｉ Ｉ。采用磷酸钙－ Ｄ Ｎ Ａ 共沉淀法将重组质粒转染 Ｈｅ Ｌａ 细胞进行体外表达, 对表达产物进行 Ｓ Ｄ Ｓ－ Ｐ Ａ Ｇ Ｅ、 Ｄｏｔ－ Ｅ Ｌ Ｉ Ｓ Ａ 和 Ｗｅｓｔｅｒｎ － ｂｌｏｔ 鉴定。结果　表达产物占表达蛋白总量的１６４ ％ , 相对分子量与预设计的４８ｋ Ｄａ 基本相符。表达产物与鼠抗恶性疟原虫血清及构建的重组质粒免疫鼠血清产生特异免疫反应。结论　表达载体 Ｐ Ｃ Ｄ Ｎ Ａ３ 在 Ｈｅ Ｌａ 细胞内可表达出具有一定免疫学活性的恶性疟原虫重组抗原蛋白。     

mRNA and protein localization of the IGF system during mouse embryonic development in areas with apoptosis.

We analysed mRNA and protein localization of the IGF system components in regions with apoptosis during mouse development between 9.5 and 13.5 days post coitum. A spatio-temporal relationship between these expression patterns and the onset of apoptosis in specific areas was sought. The IGFBP mRNA and protein expression patterns were tissue-specific. In most tissues, mRNA expression patterns colocalized with protein localization. Discrepancies between mRNA and protein detection were found in, for example, lens, neural layer of the retina, whiskers and somites. Localization of the IGFs, the type I IGF receptor and IGFBP-2 correlated well with cell death regions. When these genes were expressed no apoptosis occurred and vice versa. Correlation of IGFBP-3, -4 and -5 with apoptosis regions was noticed only at 13.5 days post coitum. In eye muscles, whiskers and somites, the expression of IGF system components preceded the occurrence of apoptotic cells. When IGF-I expression ceased, apoptosis occurred in these areas. In conclusion, our results suggest that IGF-I, the type I IGF receptor and IGFBP-2 inhibit apoptosis. In contrast, IGFBP-3, -4 and -5 may stimulate apoptosis by trapping the IGFs. Tissue-specific modulation of IGF protective action against apoptosis by the different IGFBPs during mouse embryonal development may contribute to organ specific morphology.     

Characterization of insulin-like growth factor binding proteins (IGFBP) and regulation of IGFBP-4 in bone marrow stromal cells

Summary. Bone marrow stromal cells synthesize and secrete insulin-like growth factor (IGF)-I and IGF-binding proteins (IGFBP). IGFBPs may modulate the action of IGF-I or IGF-II on haemopoiesis. However, the specific IGFBPs produced by various stromal cell types have not been identified. We examined six different stromal phenotypes for IGFBP protein and IGFBP-1 to -6 mRNA expression. [¹²⁵I]IGF-I ligand blot analysis of conditioned medium demonstrate different patterns of IGFBP secretion by each cell type. The most prominent IGFBPs were 24 and 29 kD species, consistent with IGFBP4 and IGFBP5, respectively. RNase protection assays demonstrate that, overall, stromal cells express IGFBP-2 to -6 mRNAs, with IGFBP4, IGFBP5 and IGFBP6 mRNAs predominating. Since agents that modulate cAMP levels may influence haemopoiesis via the release of stromal-derived cytokines, we determined the effect of forskolin, a cAMP agonist, on IGFBP4 expression in TC-1 cells. Forskolin (10 ⁵ M) up-regulated IGFBP4 mRNA and protein secretion in a time-dependent manner. These findings suggest that IGFBP-4, -5 and -6 released by stromal cells may be key modulators of the haemopoietic response to IGFs. Release of IGFBP4 by agents that increase cAMP may be an important mechanism involved in regulating IGF bioavailability in the marrow microenvironment.     

Specifying the cellular responses to IGF signals: roles of IGF-binding proteins

Regulation of peptide growth factor/hormone activities by secreted hormone-binding proteins has emerged as a common theme in cell-cell signaling. Among the best-studied examples are members of the IGF-binding protein (IGFBP) gene family. These secreted proteins bind the IGF ligands with equal or even greater affinities than do the IGF receptors, and therefore are placed in a critical regulatory position between IGFs and their cell surface receptors. The circulating IGF/IGFBP complexes prolong the half-lives of IGFs and buffer the potential hypoglycemic effects of IGFs. Locally expressed IGFBPs provide a means of localizing IGFs in specific cells and can alter the IGF biological activity. While some members of the IGFBP gene family have been consistently shown to inhibit IGF actions by preventing them from gaining access to the IGF receptors, others potentiate IGF actions by facilitating the ligand-receptor interaction. Furthermore, recent studies indicate that some IGFBPs can regulate several cellular processes through ligand-independent mechanisms. This review will focus on the roles of IGFBPs in vascular smooth muscle cells. A conceptual model of the molecular mechanisms by which IGFBPs act to determine the specific physiological outcomes of IGF stimulation is proposed and discussed.     

Anatomy of the pituitary insulin-like growth factor system.

In situ hybridization was used to map patterns of gene expression for components of the insulin-like growth factor (IGF) system, including IGF-I and -II, IGF-binding proteins 1-5 (IGFBP1-5), the IGF-I receptor, and GH in the rat pituitary. IGF-I mRNA was concentrated in isolated cells scattered throughout the gland with features typical of nonendocrine folliculo-stellate cells. IGF-II mRNA was abundant in neural (NL) and intermediate lobe (IL) capillaries, and low levels were present in endocrine cells of anterior lobe (AL) and IL. IGFBP1 mRNA was not detected in the pituitary. IGFBP2 mRNA was concentrated in epithelial cells lining AL follicles and in astroglial-like cells (pituicytes) of the NL. IGFBP3 mRNA was localized in isolated cells scattered throughout the AL and NL. IGFBP4 mRNA was relatively abundant in NL pituicytes and was diffusely expressed in the AL. IGFBP5 mRNA was equally abundant in NL and AL, and was localized in folliculo-stellate and epithelial cells of the AL and pituicytes and capillaries of the NL. Neither IGF-I nor IGFBP1-5 were detected in the IL. IGF-I receptor mRNA was abundant and homogeneously distributed throughout the AL and IL, compatible with expression by endocrine cells. There was overlap, but no particular correlation, between IGF system gene expression and GH-producing cells, which were clustered in the dorsal-lateral wings of the AL. In summary, IGF system gene expression is bountiful in the rat pituitary, but does not correlate with sites of GH synthesis. IGF-I receptor mRNA, which might have been expected to localize to somatotrophs, appears to be equally abundant in all of the endocrine cells of both AL and IL; the other constituents of the IGF system are localized in connective tissue and support elements that demonstrate no special anatomical relationship to somatotrophs. Finally, there is remarkably abundant gene expression for IGFBP2, -4, and -5 in the NL.     

Perinatal hypoxia-ischemia decreased neuronal but increased cerebral vascular endothelial IGFBP3 expression

In adults, insulin-like growth factor binding protein 3 (IGFBP3) is the main carrier protein for circulating insulin-like growth factors (IGFs) (IGF-I and-II). While most IGFBP3 is synthesized in the liver, it is also expressed locally by many cell types including vascular endothelial cells. The regulation of this endothelial IGFBP3 expression, especially in response to hypoxic-ischemic injury, has not been investigated in vivo. Using in situ hybridization histochemistry, we studied the cellular distribution of IGFBP3 mRNA in rat brains following hypoxic-ischemic injury at 1, 5, 24, and 72 h of recovery. In normal P7 rat brain, IGFBP3 mRNA was found in neurons within the thalamus, hippocampus, and amygdaloid. Low levels of IGFBP3 mRNA were also detected in cerebral vascular endothelial cells. After the hypoxic-ischemic injury, the levels of neuronal IGFBP3 mRNA substantially decreased within 24 h in areas that were normally supplied by the middle cerebral artery. In the meantime, there was an immediate increase in IGFBP3 expression in vascular endothelial cells throughout the affected hemisphere. This vascular IGFBP3 expression was further enhanced with the highest level at 24h of recovery whereas neuronal IGFBP3 expression was further decreased. By 72 h of recovery, IGFBP3 was no longer expressed in vascular endothelial cells. Taken together, the activation of IGFBP3 is a likely mechanism by which vascular endothelial cells respond to hypoxic-ischemic insult. In addition, increased endothelial IGFBP3 may modulate the interaction of IGFs with IGF-I receptors at the site of injury and/or act independently on endothelial cell growth.     

Insulin-like growth factors (IGFs), IGF receptors, and IGF-binding proteins in primary cultures of prostate epithelial cells.

Insulin-like growth factors (IGFs) are potent mitogens that bind with high affinity and specificity to IGF receptors and IGF-binding proteins (IGFBPs). We studied the roles of these three groups of proteins in prostate epithelial cells (PEC) in primary culture grown under serum-free conditions. Affinity cross-linking of IGF-I and IGF-II to crude membranes prepared from PEC revealed an abundance of type 1 IGF receptors and no evidence of type 2 IGF receptors. Western ligand blots of conditioned media (CM) from PEC demonstrated the presence of two specific IGFBP bands similar to those previously demonstrated in seminal plasma, with approximate mol wt of 31 and 24 kDa. The 31-kDa band was immunoprecipitable with an antibody to IGFBP-2, and neither band could be deglycosylated with endoglycosidase-F. Northern blot analysis of poly(A)+ RNA prepared from PEC with cDNAs for hIGFBP-1, -2, and -3 documented the expression of mRNA for hIGFBP-2 only. Modifications of the serum-free conditions of PEC did not significantly alter the IGFBP profile of PEC CM. The ability of IGF-I, IGF-II, and insulin to stimulate clonal growth of PEC was examined. IGF-I stimulated PEC growth with an ED50 of 0.1 ng/mL. IGF-II and insulin, respectively, were 1 and 3 orders of magnitude less effective than IGF-I in stimulating the growth of PEC. Radioimmunoassayable IGF-I and IGF-II levels in PEC CM were below the assay detection levels. In conclusion, we suggest that IGFs are important growth stimulators of PEC in culture, that their actions are mediated through the type 1 IGF receptor, and that PEC produce hIGFBP-2 and a 24-kDa IGFBP which may modulate IGF action in these cells.     

Regulation of insulin-like growth factor binding protein synthesis and secretion in a bovine epithelial cell line.

The Madin-Darby bovine kidney cell line was used to examine regulation of insulin-like growth factor binding protein (IGFBP) synthesis by epithelial cells. Ligand and immunoblot analysis of conditioned media indicated that IGFBP-2 was the predominant IGFBP secreted by untreated cells. Treatment with forskolin decreased secretion of IGFBP-2 by 75 +/- 3% and induced the appearance of IGFBP-3 and 24,000 Mr IGFBP. Although insulin alone did not induce the appearance of either band, in the presence of forskolin it increased the IGFBP-3 and 24,000 Mr bands 4.2 +/- 1.1 and 7.3 +/- 0.9-fold, respectively, above the values for forskolin treatment alone. Exposure to forskolin resulted in a 3-fold decrease in the abundance of IGFBP-2 messenger RNA (mRNA), and a 30-fold increase in IGFBP-3 mRNA. An additional 2- to 3-fold increase in IGFBP-3 mRNA was observed when cells were treated with insulin plus forskolin. Treatment with insulin plus forskolin increased cell number 2-fold, compared to small increases (26%) observed with forskolin treatment alone. Since treatment with IGF-I or -II did not result in similar responses to those of insulin, IGF analogs with differing affinities for IGFBP and IGF type I receptor were tested. B-chain IGF-I (decreased affinity for IGFBP) increased cell number and enhanced forskolin's effects on IGFBP-3 secretion and mRNA abundance to the same extent as insulin, whereas [Leu24,1-62]IGF-I (decreased affinity for the type I IGF receptor) did not. Therefore, activation of the type I IGF receptor was required to elicit increases in cell number and IGFBP synthesis and secretion, and the actions of IGF-I and II were likely blocked by binding to the large amounts of IGFBP-2 that were secreted. These results are in direct contrast to studies with human fibroblasts in which IGF-I and [Leu24,1-62]IGF-I stimulate IGFBP-3 secretion, whereas B-chain IGF-I has only a minimal effect. The ability to differentially regulate secretion of different forms of IGFBPs by epithelial cells and the finding that regulation is distinct from that of fibroblasts may have important implications for understanding mechanisms by which IGFs and IGFBPs interact to regulate epithelial cell growth.     

Regulatory Actions of Insulin-like Growth Factor-binding Proteins.

The six insulin-like growth factor-binding proteins (IGFBPs) are important regulators of insulin-like growth factor (IGF) action. Circulating high molecular weight complexes that contain IGF and IGFBP-3 restrict IGF bioavailability, and excess IGFBPs inhibit IGF action by forming biologically inactive complexes. IGFs can be released from these complexes by proteolysis. Potentiation of IGF activity might occur under specific circumstances, and involves the slow dissociation of IGFs from IGFBP complexes localized in the pericellular space, whose affinity has been reduced by dephosphorylation or association with the cell surface or extracellular matrix. Several IGFBPs or IGFBP fragments also have activities that do not involve IGFs or IGF receptors. The mechanisms by which IGFBPs regulate IGF action and exert their independent actions will be examined.     

Insulin and insulin-like growth factors (IGFs) stimulate production of IGF-binding proteins by ovarian granulosa cells.

Ligand blot analysis of granulosa cell (GC)-conditioned culture medium revealed several easily measurable insulin-like growth factor (IGF)-binding proteins (IGFBPs), including IGFBP-3 [40-44 kilodaltons (kDa)] and IGFBP-2 (34 kDa). In the present study, IGF-I, in a dose-dependent manner, significantly stimulated the production of these IGFBPs. Insulin, but not IGF-II, mimicked IGF-I's action on IGFBP-3 and -2 production, but was less potent. The synthetic IGF, long R3-IGF-I, which has very low affinity for IGFBPs and only slightly reduced affinity for the IGF-I (type I) receptor, had significantly greater potency in stimulating IGFBP-3 and -2 production compared to IGF-I. Des-(1-3)-IGF-I had similar effects. IGF-I, IGF-II, and the IGF-I analogs, but not insulin, also induced production of an unidentified 30-kDa IGFBP not normally detectable in these cultures. However, in the presence of epidermal growth factor (which was without independent effect on the 30-kDa IGFBP), insulin also induced this 30-kDa IGFBP. By Northern analysis the expression of IGFBP-3 mRNA was found to be significantly stimulated by IGF-I. In summary, insulin stimulated IGFBP-3 and -2 production in a manner that mimics that of IGF-I and the more potent long R3-IGF-I. However, its low potency suggested that IGFBP production is regulated via the IGF-I (type I) receptor. The much higher potency of long R3-IGF-I compared to that of IGF-I suggests that the IGFBPs themselves modulate the action of IGFs by sequestering exogenous IGFs. Thus, one cellular response to IGF stimulation is the production of IGFBPs, which, in turn, reduce or negate the biological activity of the IGFs. The effects of insulin-like peptides are exerted at least in part by increasing levels of mRNA for specific BPs.