Rosolowsky L J, Campbell W B
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75235-9041.
Am J Physiol. 1994 Jan;266(1 Pt 1):E107-17. doi: 10.1152/ajpendo.1994.266.1.E107.
Intra-adrenal factors promote basal as well as adrenocorticotropic hormone (ACTH)-, angiotensin-, and flow-induced steroid secretion. Because endothelial cells respond to changes in flow and are in a close anatomical relationship to steroidogenic cells, we examined the effect of endothelial cells on the secretion of aldosterone from zona glomerulosa (ZG) cells. Endothelial cells and endothelial cell-conditioned medium (EC-CM) stimulated the release of aldosterone from ZG cells. The stimulatory effect was related to the concentration of endothelial cells or EC-CM. The maximal stimulatory effect was 60-70% of the maximal effect of ACTH. Endothelial cells alone did not produce aldosterone. Human fibroblasts were ineffective in promoting aldosterone release. Endothelial cells and EC-CM failed to stimulate cortisol release from zona fasciculata cells. Treatment of the EC-CM with trypsin and pronase abolished the activity, indicating that a protein mediated the effect. However, the EC-CM activity could be distinguished from angiotensin, endothelin-1, and bradykinin. The factor stimulated the formation of pregnenolone but not the conversion of corticosterone to aldosterone. This endothelium-derived steroidogenic factor appeared to be a novel stimulus to aldosterone secretion. This study represents the first demonstration that endothelial cells alter endocrine function in vitro.
肾上腺内因子可促进基础状态下以及促肾上腺皮质激素(ACTH)、血管紧张素和血流诱导的类固醇分泌。由于内皮细胞对血流变化有反应,且在解剖学上与类固醇生成细胞关系密切,我们研究了内皮细胞对球状带(ZG)细胞醛固酮分泌的影响。内皮细胞和内皮细胞条件培养基(EC-CM)可刺激ZG细胞释放醛固酮。刺激作用与内皮细胞或EC-CM的浓度相关。最大刺激作用为ACTH最大作用的60%-70%。单独的内皮细胞不产生醛固酮。人成纤维细胞对促进醛固酮释放无效。内皮细胞和EC-CM不能刺激束状带细胞释放皮质醇。用胰蛋白酶和链霉蛋白酶处理EC-CM可消除其活性,表明一种蛋白质介导了该作用。然而,EC-CM的活性可与血管紧张素、内皮素-1和缓激肽相区分。该因子刺激孕烯醇酮的形成,但不刺激皮质酮向醛固酮的转化。这种内皮源性类固醇生成因子似乎是醛固酮分泌的一种新刺激物。本研究首次证明内皮细胞在体外可改变内分泌功能。