Holzwarth M A, Gomez-Sanchez C E, Engeland W C
Department of Molecular and Integrative Physiology, University of Illinois, Urbana 61801, USA.
Endocr Res. 1996 Nov;22(4):401-6. doi: 10.1080/07435809609043724.
The phenotype of the proliferating cells during adrenocortical growth has remained controversial although glomerulosa, fasciculata and intermediate zone cells have all been considered possible candidates. This was due in part to the inability to identify specific adrenocortical cell types in comparing different types of growth. In the present studies, using immunocytochemical localization of cytochrome P450 aldosterone synthase (P450aldo) and cytochrome P450 11 beta-hydroxylase (P45011 beta) to identify adrenocortical cell phenotypes as well as Ki-67 to label proliferating cells, we have investigated the phenotype of the proliferating cells in the compensatory adrenal growth response to unilateral adrenalectomy. Between 24 and 96 hrs after unilateral adrenalectomy, most Ki-67(+) nuclei were found in the outermost region of the fasciculata, as defined by P45011 beta immunoreactive cells. Few Ki-67(+) nuclei were found in the glomerulosa, defined by P450aldo cells or in the z intermedia, identified by the absence of both P450aldo and P45011 beta. To test which cell type is activated by unilateral adrenalectomy, we altered the phenotypic configuration of the adrenal cortex; rats were placed on a low Na+ diet for three weeks, resulting in a marked expansion of the number of P450aldo(+) cells. An abundance of proliferating cells was identified primarily in the expanded glomerulosa, but not in the intermedia or fasciculata. In contrast, the proliferation associated with compensatory growth in these low Na+ rats, was localized primarily in the outer P45011 beta(+) zone. These findings suggest that the phenotype of the proliferating cell is specific to the growth promoting stimulus.
尽管球状带、束状带和中间带细胞都被认为可能是肾上腺皮质生长过程中增殖细胞的候选类型，但增殖细胞的表型一直存在争议。部分原因是在比较不同类型的生长时，无法识别特定的肾上腺皮质细胞类型。在本研究中，我们利用细胞色素P450醛固酮合成酶（P450aldo）和细胞色素P450 11β-羟化酶（P45011β）的免疫细胞化学定位来识别肾上腺皮质细胞表型，并利用Ki-67标记增殖细胞，研究了单侧肾上腺切除术后代偿性肾上腺生长反应中增殖细胞的表型。在单侧肾上腺切除术后24至96小时之间，大多数Ki-67（+）细胞核位于由P45011β免疫反应性细胞界定的束状带最外层区域。在由P450aldo细胞界定的球状带或由P450aldo和P45011β均缺失所识别的中间带中，很少发现Ki-67（+）细胞核。为了测试哪种细胞类型被单侧肾上腺切除术激活，我们改变了肾上腺皮质的表型结构；将大鼠置于低钠饮食三周，导致P450aldo（+）细胞数量显著增加。大量增殖细胞主要在扩张的球状带中被识别，但在中间带或束状带中未发现。相反，这些低钠大鼠代偿性生长相关的增殖主要位于外侧P45011β（+）区。这些发现表明，增殖细胞的表型对生长促进刺激具有特异性。
