Marzouk H F, Hofland L J, den Holder F H, van Koetsveld P M, Steenbergen J, Zuiderwijk J, Abou-Hashim E M, el-Kannishy M H, de Jong F H, Lamberts S W
Department of Medicine Erasmus University, Rotterdam, The Netherlands.
Mol Cell Endocrinol. 1990 Aug 20;72(2):95-102. doi: 10.1016/0303-7207(90)90099-t.
Suramin is a polyanionic compound which has been used in the treatment of trypanosomiasis and acquired immunodeficiency syndrome (AIDS), while preliminary success has been reported in the treatment of cancer. However, suramin also causes adrenal insufficiency. We have previously reported that suramin selectively inhibited corticotropin (ACTH)-stimulated corticosterone release by dispersed adrenal cells in a dose-dependent manner via a direct interaction with the ACTH molecule. The present study was undertaken in order to investigate the effect of suramin on hormone release by dispersed rat anterior pituitary cells. Suramin at a concentration of 100 microM inhibited both basal and secretagogue-stimulated ACTH release by cells cultured in minimal essential medium (MEM) only, while it had no effect on ACTH release by cells cultured in MEM + 10% fetal calf serum (FCS) or MEM + 0.1% bovine serum albumin (BSA). In addition, suramin also caused a parallel decrease of prolactin (PRL) and growth hormone (GH) release by cells cultured in MEM only, suggesting a toxic, rather than a selective effect of suramin on anterior pituitary cells cultured in MEM only. In addition, suramin potentiated the effect of thyrotropin-releasing hormone (TRH) on PRL release by cells cultured in MEM + 10% FCS and suppressed the inhibitory effect of dopamine (DA) on PRL release by cells cultured in MEM + 10% FCS and in MEM + 0.1% BSA. Comparable suppressive effects of suramin on growth hormone-releasing hormone (GHRH)-stimulated and somatostatin (SRIH)-inhibited GH release were found in cells cultured in MEM + 0.1% BSA but not in cells cultured in MEM + 10% FCS.(ABSTRACT TRUNCATED AT 250 WORDS)
苏拉明是一种多阴离子化合物,已用于治疗锥虫病和获得性免疫缺陷综合征(艾滋病),同时在癌症治疗方面也有初步成功的报道。然而,苏拉明也会导致肾上腺功能不全。我们之前报道过,苏拉明通过与促肾上腺皮质激素(ACTH)分子直接相互作用,以剂量依赖的方式选择性抑制分散的肾上腺细胞中ACTH刺激的皮质酮释放。本研究旨在探讨苏拉明对分散的大鼠垂体前叶细胞激素释放的影响。仅在最低限度基本培养基(MEM)中培养的细胞,100微摩尔浓度的苏拉明抑制基础和促分泌剂刺激的ACTH释放,而对在MEM + 10%胎牛血清(FCS)或MEM + 0.1%牛血清白蛋白(BSA)中培养的细胞的ACTH释放没有影响。此外,苏拉明还使仅在MEM中培养的细胞的催乳素(PRL)和生长激素(GH)释放平行减少,这表明苏拉明对仅在MEM中培养的垂体前叶细胞具有毒性而非选择性作用。此外,苏拉明增强了促甲状腺激素释放激素(TRH)对在MEM + 10% FCS中培养的细胞PRL释放的作用,并抑制了多巴胺(DA)对在MEM + 10% FCS和MEM + 0.1% BSA中培养的细胞PRL释放的抑制作用。在MEM + 0.1% BSA中培养的细胞中发现苏拉明对生长激素释放激素(GHRH)刺激的和生长抑素(SRIH)抑制的GH释放有类似的抑制作用,但在MEM + 10% FCS中培养的细胞中未发现。(摘要截短至250字)