LOCALIZATION OF CYP2D16 IN THE GUINEA-PIG ADRENAL-CORTEX BY IMMUNOHISTOCHEMISTRY AND IN-SITU HYBRIDIZATION

Recent reports indicate that the cytochrome P450 isozyme, CYP2D16, is expressed at high levels in the inner regions of the guinea pig adrena l cortex and may contribute to xenobiotic and/or steroid metabolism in the gland. In the present studies, immunohistochemical and in situ hy bridization techniques were employed to definitively establish the loc alization of CYP2D16 within the adrenal cortex. In male guinea pigs of various ages, CYP2D16 protein and mRNA were highly localized to the z ona reticularis (ZR); none was detectable in the zona fasciculata (ZF) , zona glomerulosa (ZG) or the medulla. In contrast, the steroidogenic P450 isozyme, CYP17, was distributed throughout the ZF and ZR. From t he earliest stages of development of the ZR, CYP2D16 staining was inte nse. As guinea pigs aged, the ZR progressively enlarged and comprised a proportionately greater amount of the cortex. At all ages, CYP2D16 w as uniformly distributed throughout only the ZR. Coinciding with the a ge-related growth of the ZR and increase in adrenal CYP2D16 content wa s an increase in adrenal xenobiotic-metabolizing activity. The results establish that CYP2D16 has an intraadrenal localization that is uniqu e among P450 isozymes, suggesting novel regulatory mechanisms and indi cating that CYP2D16 may serve as a specific marker for ZR cells. The i ncrease in CYP2D16 expression with age probably accounts for increasin g levels of xenobiotic metabolism and may also contribute to an increa se in intraadrenal cortisol degradation in older animals. (C) 1997 Els evier Science Ireland Ltd.