Haidan A, Bornstein S R, Glasow A, Uhlmann K, Lübke C, Ehrhart-Bornstein M
Department of Internal Medicine III, University of Leipzig, Germany.
Endocrinology. 1998 Feb;139(2):772-80. doi: 10.1210/endo.139.2.5740.
Historically, catecholamine-producing chromaffin cells and steroid-producing adrenocortical cells have been regarded as two independent endocrine systems that are united under a common capsule to form the adrenal gland. There is increasing evidence for bidirectional interactions, with regulatory influences of adrenocortical secretory products on adrenomedullary functions and vice versa. However, the direct involvement of chromaffin cells on the regulation and maintenance of cortical function has not yet been demonstrated. Therefore, we analyzed glucocorticoid secretion and P450 messenger RNA (mRNA) expression in bovine adrenocortical cells in cocultures with chromaffin cells compared with those in pure cortical cell cultures. Cortisol release from cortical cells in coculture with chromaffin cells was 10 times as high (mean +/- SEM, 1035 +/- 119%) as that from the same number of isolated cortical cells (100 +/- 11%). By a [3H]thymidine incorporation assay, it was demonstrated that this effect was not due to a higher proliferation rate. Northern analysis revealed an increasing expression of P450(17alpha) mRNA in the coculture from days 1-5, whereas in isolated cortical cells, P450(17alpha) mRNA decreased, leading to a 6-fold difference on day 5. Inhibitors of protein (cycloheximide) or RNA (actinomycin D) synthesis completely annulled the observed increase in cortisol release, indicating that de novo protein synthesis is required for this activation of adrenocortical steroidogenesis. Addition of the cyclooxygenase inhibitor indomethacin reduced the stimulatory effect, suggesting that this stimulation is in part mediated by PGs. Locally produced ACTH, catecholamines, and interleukin-1 accounted for 43% of the effect. Secretory products of chromaffin cells that act in concert are believed to be responsible for the stimulation of steroidogenesis in the coculture. The coculture system is an in vitro model that corresponds to the in vivo situation in the intact adrenal gland, where both endocrine cell systems are in close contact. Our data demonstrate the requirement of intraadrenal cellular communication for the full strength of the adrenocortical hormonal response.
从历史上看，产生儿茶酚胺的嗜铬细胞和产生类固醇的肾上腺皮质细胞一直被视为两个独立的内分泌系统，它们在一个共同的被膜下联合形成肾上腺。越来越多的证据表明存在双向相互作用，肾上腺皮质分泌产物对肾上腺髓质功能有调节作用，反之亦然。然而，嗜铬细胞对皮质功能的调节和维持的直接参与尚未得到证实。因此，我们分析了与嗜铬细胞共培养的牛肾上腺皮质细胞中糖皮质激素的分泌以及P450信使核糖核酸（mRNA）的表达，并与纯皮质细胞培养物中的情况进行了比较。与嗜铬细胞共培养的皮质细胞中皮质醇的释放量是相同数量的分离皮质细胞释放量的10倍（平均值±标准误，1035±119%对100±11%）。通过[3H]胸腺嘧啶掺入试验表明，这种效应并非由于增殖率较高。Northern分析显示，在共培养的第1至5天，P450(17α)mRNA的表达增加，而在分离的皮质细胞中，P450(17α)mRNA减少，在第5天导致6倍的差异。蛋白质（放线菌酮）或RNA（放线菌素D）合成抑制剂完全消除了观察到的皮质醇释放增加，表明肾上腺皮质类固醇生成的这种激活需要从头合成蛋白质。添加环氧化酶抑制剂吲哚美辛降低了刺激作用，表明这种刺激部分是由前列腺素介导的。局部产生的促肾上腺皮质激素、儿茶酚胺和白细胞介素-1占该效应的43%。据信，共同起作用的嗜铬细胞分泌产物是共培养中类固醇生成刺激的原因。共培养系统是一种体外模型，与完整肾上腺中的体内情况相对应，在体内两种内分泌细胞系统紧密接触。我们的数据表明，肾上腺内细胞间通讯对于肾上腺皮质激素反应的充分强度是必需的。
