Maintenance of cell proliferation and steroidogenesis in cultured human fetal adrenal cells chronically exposed to adrenocorticotropic hormone: rationalization of in vitro and in vivo findings.
Maintenance of cell proliferation and steroidogenesis in cultured human fetal adrenal cells chronically exposed to adrenocorticotropic hormone: rationalization of in vitro and in vivo findings.
复制标题
DOI：
10.1095/biolreprod42.4.683
复制
发表时间：
1990-04
影响因子：
3.6
通讯作者：
A. Di Blasio;D. Fujii;M. Yamamoto;M. Martín;R. Jaffe
中科院分区：
文献类型：
--
作者：
A. Di Blasio;D. Fujii;M. Yamamoto;M. Martín;R. Jaffe
以往的研究表明，肾上腺细胞急性暴露于促肾上腺皮质激素(ACTH)可显着刺激体外合成类固醇的能力，但也抑制细胞的增殖。然而，在体内，ACTH被认为可以刺激肾上腺细胞的生长。为了解决这一差异，我们确定了长期(9-11天)连续或间歇性暴露于ACTH对人胎儿肾上腺细胞增殖和类固醇生成的影响。本文对妊娠18~22周的胎儿肾上腺进行了研究。将胎带细胞接种于塑料或细胞外基质(ECM)上，加入或不加入碱性成纤维细胞生长因子(BFGF)(0.5 ng/ml)和1或10 nM ACTH。细胞计数结果显示，碱性成纤维细胞生长因子在培养的第9天内刺激细胞增殖。在碱性成纤维细胞生长因子的存在下，塑料的平均倍增时间从44 h缩短到30 h，ECM的平均倍增时间从37 h减少到26 h。在此条件下，ACTH不抑制细胞增殖。用3-β-羟基类固醇脱氢酶(3-β-HSD)组织化学染色检测ACTH处理后胎儿肾上腺皮质激素分泌细胞的增殖情况。在培养的第5~9天，阳性细胞数增加了4倍以上。在培养的前5天，用1 NM的ACTH连续处理使脱氢表雄酮硫酸酯(DHAS)的产量增加5-10倍。此后，刺激的激素产生随着时间的推移而减少，尽管在9天结束时，对照组和ACTH处理的培养物之间仍然有近100倍的差异。
Previous studies indicated that acute exposure of adrenal cells to adrenocorticotropic hormone (ACTH) markedly stimulates steroidogenic capacity in vitro but also inhibits cell proliferation. However, in vivo, ACTH is known to stimulate adrenal cell growth. To address this discrepancy, we determined the effect of long-term (9-11 days) continuous or intermittent exposure to ACTH on human fetal adrenal cell proliferation and steroidogenesis. Adrenal glands from fetuses 18-22 wk gestation were studied. Fetal zone cells were plated either on plastic or on an extracellular matrix (ECM) in the presence and absence of basic fibroblast growth factor (bFGF) (0.5 ng/ml) and 1 or 10 nM ACTH. As determined by cell counting, bFGF stimulated cell proliferation during 9 days in culture. In the presence of bFGF, the average doubling time decreased from 44 to 30 h on plastic and from 37 to 26 h on ECM. Under these conditions, ACTH did not inhibit cell proliferation. Proliferation of fetal adrenal corticosteroid-producing cells in the ACTH-treated cultures also was assessed by histochemical staining for 3 beta-hydroxysteroid dehydrogenase (3 beta HSD). The number of positive cells increased more than 4-fold between Days 5 and 9 in culture. Continuous treatment with 1 nM ACTH increased dehydroepiandrosterone sulfate (DHAS) production 5- to 10-fold during the first 5 days in culture. Thereafter, the stimulated hormone production decreased over time, although there was still a difference of almost 100-fold between the control and ACTH-treated cultures at the end of 9 days.(ABSTRACT TRUNCATED AT 250 WORDS)