Pellerin S, Keramidas M, Chambaz E M, Feige J J
INSERM U-244, Biochemistry of Endocrine Cell Regulations, Department of Molecular and Structural Biology, Commissariat á l'Energie Atomique (Atomic Energy Committee) Grenoble, France.
Endocrinology. 1997 Mar;138(3):1321-7. doi: 10.1210/endo.138.3.4962.
The adult mammalian adrenal cortex undergoes permanent regeneration. This process implies a cellular proliferation step restricted to the external zone of the tissue, and a subsequent centripetal cell migration during which phenotypic transition from glomerulosa into fasciculata and reticularis cells and elimination of senescent cells through apoptosis occur. As the molecular mechanisms implied in adrenocortical cell migration are still generally unknown, we addressed that question in the present study. Of several extracellular matrix proteins tested, laminin was the most potent chemotactic and haptotactic factor for bovine fasciculata adrenocortical cells. The maximal chemotactic effect (3-fold stimulation) was observed with 50-75 micrograms/ml laminin, whereas the haptotactic effect (3.5-fold stimulation) plateaued for laminin concentrations in the coating solution over 25 micrograms/ml. Using an anti-Engelbreth-Holm-Swarm laminin antibody, we could demonstrate that adrenocortical cells actively synthesize and secrete Engelbreth-Holm-Swarm-laminin, with the A chain produced in limiting quantities. ACTH treatment of adrenocortical cells specifically induced a 2.7- to 4.5-fold increase in A chain synthesis, resulting in a corresponding increase in the amount of secreted laminin. The distribution of laminin in the adrenal cortex tissue was then evaluated by standard immunohistochemistry. The protein appeared to be uniformly expressed in the three zones of the cortex. This observation does not favor the hypothesis that laminin acts as an attractant driving centripetal cell migration. Laminin, which is synthesized under the control of the systemic hormone ACTH, appears as a permissive factor that facilitates proper homeostasis of the adrenocortical tissue.
成年哺乳动物的肾上腺皮质会经历永久性再生。这一过程意味着细胞增殖步骤局限于组织的外层区域，随后是向心细胞迁移，在此过程中会发生从球状带细胞向束状带和网状带细胞的表型转变，以及通过凋亡清除衰老细胞。由于肾上腺皮质细胞迁移所涉及的分子机制仍普遍未知，我们在本研究中探讨了这个问题。在测试的几种细胞外基质蛋白中，层粘连蛋白是对牛束状带肾上腺皮质细胞最有效的趋化因子和趋触因子。用50 - 75微克/毫升的层粘连蛋白可观察到最大趋化作用（3倍刺激），而当包被溶液中层粘连蛋白浓度超过25微克/毫升时，趋触作用（3.5倍刺激）趋于平稳。使用抗恩格尔布雷特 - 霍尔姆 - 斯旺层粘连蛋白抗体，我们能够证明肾上腺皮质细胞能主动合成并分泌恩格尔布雷特 - 霍尔姆 - 斯旺层粘连蛋白，其中A链产量有限。促肾上腺皮质激素（ACTH）处理肾上腺皮质细胞可特异性诱导A链合成增加2.7至4.5倍，导致分泌的层粘连蛋白量相应增加。然后通过标准免疫组织化学评估层粘连蛋白在肾上腺皮质组织中的分布。该蛋白似乎在皮质的三个区域均匀表达。这一观察结果不支持层粘连蛋白作为驱动向心细胞迁移的吸引剂的假说。在全身性激素ACTH控制下合成的层粘连蛋白，似乎是一种促进肾上腺皮质组织正常稳态的许可因子。
