Langlais David, Couture Catherine, Kmita Marie, Drouin Jacques
Laboratoire de génétique moléculaire, Institut de recherches cliniques de Montréal (IRCM), 110, avenue des Pins Ouest, Montréal, Quebec, H2W 1R7 Canada.
Mol Endocrinol. 2013 Jul;27(7):1103-12. doi: 10.1210/me.2012-1407. Epub 2013 Jun 10.
The identification of a stable pool of progenitor/stem cells in the adult pituitary has renewed the interest of identifying mechanisms for maintenance of pituitary cells throughout life. Whereas developmental studies have shown that progenitor expansion is the major source of new differentiated cells during pituitary organogenesis, the contribution of these progenitors for maintenance of the adult tissue is not clear although progenitors were clearly involved in cell expansion following end-organ ablation, notably after adrenalectomy and/or gonadectomy. We have used a genetic trick that eliminates dividing cells by apoptosis in order to assess the contribution of differentiated corticotropes and melanotropes for maintenance of their population in the adult pituitary. The system relies on chromosome instability created by the action of the Cre recombinase on inverted loxP sites. Expression of Cre recombinase in corticotropes and melanotropes led to progressive loss of corticotropes whereas melanotropes were unaffected. Because the Cre transgene is not expressed in progenitors, the data indicate that maintenance of the adult corticotrope pool is primarily due to self-duplication of differentiated cells. In contrast, melanotropes do not divide. Maintenance of corticotropes by self-duplication contrasts with the reported proliferative response of undifferentiated cells observed after adrenalectomy. If corticotrope reentry into cell cycle constitutes a normal mechanism to maintain the adult corticotrope pool, this same mechanism may also be perturbed during corticotrope adenoma development in Cushing's disease.
成体垂体中祖细胞/干细胞稳定池的鉴定，重新激发了人们对确定终生维持垂体细胞机制的兴趣。发育研究表明，在垂体器官发生过程中，祖细胞扩增是新分化细胞的主要来源，尽管在终末器官切除后，特别是肾上腺切除术和/或性腺切除术后，祖细胞明显参与了细胞扩增，但这些祖细胞对成体组织维持的贡献尚不清楚。我们采用了一种基因策略，通过凋亡消除分裂细胞，以评估分化的促肾上腺皮质激素细胞和促黑素细胞对成体垂体中其细胞群维持的贡献。该系统依赖于由Cre重组酶作用于反向loxP位点产生的染色体不稳定性。促肾上腺皮质激素细胞和促黑素细胞中Cre重组酶的表达导致促肾上腺皮质激素细胞逐渐减少，而促黑素细胞不受影响。由于Cre转基因在祖细胞中不表达，数据表明成体促肾上腺皮质激素细胞池的维持主要是由于分化细胞的自我复制。相比之下，促黑素细胞不分裂。通过自我复制维持促肾上腺皮质激素细胞与肾上腺切除术后观察到的未分化细胞的增殖反应形成对比。如果促肾上腺皮质激素细胞重新进入细胞周期是维持成体促肾上腺皮质激素细胞池的正常机制，那么在库欣病促肾上腺皮质激素细胞腺瘤发生过程中，这一相同机制也可能受到干扰。
