Yaglova Natalya V, Tsomartova Dibakhan A, Obernikhin Sergey S, Nazimova Svetlana V, Ivanova Marina Y, Chereshneva Elizaveta V, Yaglov Valentin V, Lomanovskaya Tatiana A
Laboratory of Endocrine System Development, Federal State Budgetary Institution Research Institute of Human Morphology, Moscow, Russia.
Department of Histology, Cytology, and Embryology, Federal State Funded Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University, Moscow, Russia.
Heliyon. 2021 Jan 9;7(1):e05932. doi: 10.1016/j.heliyon.2021.e05932. eCollection 2021 Jan.
Transcriptional regulation of growth, maturation, and cell turnover in adrenal cortex during postnatal development has been significantly less studied than in embryonic period, while elucidation of factors mediating its normal postnatal morphogenesis could clarify mechanisms of tumorigenesis in adrenal cortex. Expression of transcription factors Hex, β-catenin, and Wnt signaling in the adrenal cortex of male pubertal and postpubertal Wistar rats were examined. Adrenal cortex morphology and hormone production during postnatal development were also studied. Adrenocortical zones demonstrated similar reduction of Ki-67-expressing cells, but different patterns of morphological and functional changes. Age-dependent decrease in percentage of cells with membrane localization of β-catenin and stable rate of cells with nuclear β-catenin, indicative of Wnt signaling activation, were revealed in each cortical zone. Nuclear β-catenin was not observed in immature areas of zona fasciculata. No association between Wnt signaling activation and rates of proliferation as well as changes in secretion of adrenocortical hormones was observed in postnatal development of rat adrenal cortex. Hex, known as antiproliferative factor, showed up-regulation of expression after puberty. Strong inverse correlations between ratio of Hex-positive cells and proliferating cells were found in zona glomerulosa and zona fasciculata. Zona reticularis demonstrated moderate correlation. Thus, these findings suggest a role for Hex in proliferation control during postnatal development of the rat adrenal cortex and possible implication of Hex down-regulation in adrenocortical dysplasia and neoplasia, which requires further study. Evaluation of Hex expression may also be considered a potent tool in assessment of cell proliferation in rat adrenal cortex.
与胚胎期相比,出生后发育过程中肾上腺皮质生长、成熟和细胞更新的转录调控研究明显较少,而阐明介导其正常出生后形态发生的因素可能会阐明肾上腺皮质肿瘤发生的机制。研究了雄性青春期和青春期后Wistar大鼠肾上腺皮质中转录因子Hex、β-连环蛋白和Wnt信号的表达。还研究了出生后发育过程中肾上腺皮质的形态和激素产生情况。肾上腺皮质各带显示出表达Ki-67的细胞数量有类似减少,但形态和功能变化模式不同。在每个皮质带中均发现,β-连环蛋白膜定位细胞百分比随年龄下降,而核β-连环蛋白细胞比例稳定,这表明Wnt信号被激活。在束状带的未成熟区域未观察到核β-连环蛋白。在大鼠肾上腺皮质出生后发育过程中,未观察到Wnt信号激活与增殖率以及肾上腺皮质激素分泌变化之间存在关联。Hex作为抗增殖因子,在青春期后表达上调。在球状带和束状带中发现Hex阳性细胞与增殖细胞的比例呈强负相关。网状带显示出中度相关性。因此,这些发现表明Hex在大鼠肾上腺皮质出生后发育过程中的增殖控制中发挥作用,并且Hex下调可能与肾上腺皮质发育异常和肿瘤形成有关,这需要进一步研究。评估Hex表达也可被视为评估大鼠肾上腺皮质细胞增殖的有效工具。