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Altered Expression Patterns of Heterogeneous Nuclear Ribonucleoproteins A2 and B1 in the Adrenal Cortex

WenWen Wu, Hiroshi Kamma, Masachika Fujiwara, Yukiko Yano, Hiroaki Satoh, Hisatoh Hara, Tohru Yashiro, Ei Ueno and Yuji Aiyoshi

Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki, Japan (WWW,HK); Kensei General Hospital, Ibaraki, Japan (MF); and Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan (YY,HS,HH,TY,EU,YA)

Correspondence to: Hiroshi Kamma, Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan. E-mail: hkamma{at}md.tsukuba.ac.jp

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 B1 are among the abundant pre-mRNA-binding proteins involved in alternative splicing. We examined the expression of A2 and B1 in normal adrenal cortex and tumors. B1 was variably expressed in the zona fasciculata-reticularis, although A2 was diffusely expressed in the three zones. B1 was more abundant in compact cells than clear cells, and B1 expression was frequent in the zona reticularis, which consists mainly of compact cells. In three kinds of cortical adenomas autonomously producing hormones, B1 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 B1 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 B1 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.

(J Histochem Cytochem 53:487–495, 2005)

Key Words: hnRNP A2/B1 • alternative splicing • adrenal cortex • ACTH • hormonal activity

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