Bb. Yuan et al., LOCALIZATION OF CYP2D16 IN THE GUINEA-PIG ADRENAL-CORTEX BY IMMUNOHISTOCHEMISTRY AND IN-SITU HYBRIDIZATION, Molecular and cellular endocrinology, 134(2), 1997, pp. 139-146
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.