Altered expression patterns of heterogeneous nuclear ribonucleoproteins A2 and B1 in the adrenal cortex

Several proteins implicated in hormonogenesis of the adrenal cortex have alternatively spliced isoforms, which respond differently to adrenocorticotropic hormone (ACTH). Heterogeneous nuclear ribonucleoproteins A2 and 131 are among the abundant pre-mRNA-binding proteins involved in alternative splicing. We examined the expression of A2 and 131 in normal adrenal cortex and tumors. 131 was variably expressed in the zona fasciculata-reticularis, although A2 was diffusely expressed in the three zones. 131 was more abundant in compact cells than clear cells, and 131 expression was frequent in the zona reticularis, which consists mainly of compact cells. In three kinds of cortical adenomas autonomously producing hormones, 131 was generally overexpressed and there were no significant differences among them. In cortisol-producing tumors, non-tumor parts of the cortex, which were generally atrophic due to low ACTH, had less 131 protein than normal adrenals. These results suggested a correlation between B1 expression and the hormonal activity responding to ACTH. In vitro ACTH stimulation induced a biphasic expression of 131 in an H295R cortical carcinoma cell line, and it paralleled hormonogenesis. Conclusively, B1 expression varied in relation to the hormonal activity responding to the ACTH, and it may provide a key to elucidating the splicing mechanisms involved in hormonogenesis.