Sicard Flavie, Ehrhart-Bornstein Monika, Corbeil Denis, Sperber Simone, Krug Alexander W, Ziegler Christian G, Rettori Valeria, McCann Samuel M, Bornstein Stefan R
Department of Medicine, Carl Gustav Carus University Medical School, University of Technology, Dresden, Germany.
Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):2007-12. doi: 10.1073/pnas.0610898104. Epub 2007 Jan 30.
The adrenal gland comprises two endocrine tissues of distinct origin, the catecholamine-producing medulla and the steroid-producing cortex. The inner adrenocortical zone, which is in direct contact with the adrenomedullary chromaffin cells, produces dehydroepiandrostendione (DHEA) and DHEA sulfate (DHEAS). These two androgens exhibit potential effects on neurogenesis, neuronal survival, and neuronal stem cell proliferation. Unlike the closely related sympathetic neurons, chromaffin cells are able to proliferate throughout life. The aim of this study was to investigate the effect of DHEA and DHEAS on proliferation of bovine chromaffin cells from young and adult animals. We demonstrated that graded concentrations of leukemia inhibitory factor induced proliferation of chromaffin cells from young animals, whereas EGF had no effect. On the contrary, EGF increased the cell proliferation in cells from adult animals, whereas leukemia inhibitory factor was inactive. In both cases, DHEA decreased the proliferative effect induced by the growth factors. Surprisingly, DHEAS enhanced, in a dose-dependent-manner, the effect of growth factors on proliferation in cells from adult animals but not from young animals. Flutamide, ICI 182,780, and RU 486 had no effect on the action of DHEA or DHEAS on chromaffin cell proliferation. These data show that DHEA and its sulfated form, DHEAS, differentially regulate growth-factor-induced proliferation of bovine chromaffin cells. In addition, the sensitivity of chromaffin cells to different growth factors is age-dependent. Furthermore, these two androgens may act through a receptor other than the classical steroid receptors.
肾上腺由两个起源不同的内分泌组织组成，即产生儿茶酚胺的髓质和产生类固醇的皮质。肾上腺皮质的内层区域与肾上腺髓质嗜铬细胞直接接触，产生脱氢表雄酮（DHEA）和硫酸脱氢表雄酮（DHEAS）。这两种雄激素对神经发生、神经元存活和神经元干细胞增殖具有潜在影响。与密切相关的交感神经元不同，嗜铬细胞能够终生增殖。本研究的目的是探讨DHEA和DHEAS对幼年和成年动物牛嗜铬细胞增殖的影响。我们证明，分级浓度的白血病抑制因子可诱导幼年动物嗜铬细胞增殖，而表皮生长因子（EGF）则无作用。相反，EGF可增加成年动物细胞的增殖，而白血病抑制因子则无活性。在这两种情况下，DHEA均可降低生长因子诱导的增殖作用。令人惊讶的是，DHEAS以剂量依赖的方式增强了生长因子对成年动物细胞而非幼年动物细胞增殖的作用。氟他胺、ICI 182,780和RU 486对DHEA或DHEAS对嗜铬细胞增殖的作用均无影响。这些数据表明，DHEA及其硫酸化形式DHEAS对牛嗜铬细胞生长因子诱导的增殖具有不同的调节作用。此外，嗜铬细胞对不同生长因子的敏感性具有年龄依赖性。此外，这两种雄激素可能通过经典类固醇受体以外的受体发挥作用。
