Selective
Alzheimer's disease indicator-1 (seladin-1) is a novel gene with antiapoptotic activity that is down-regulated in vulnerable brain regions in
Alzheimer's disease. This gene encodes 3-beta-hydroxysterol Delta-24-reductase (DHCR24), which converts
desmosterol into
cholesterol. In the adrenal cortex, increased expression of seladin-1/DHCR24, which appears to be modulated by
ACTH, has been recently reported in
cortisol-secreting
adenomas, compared with the adjacent atrophic tissue. In our study, we measured the expression level of seladin-1/DHCR24 in
cortisol- (n = 18) and
aldosterone-secreting (n = 16)
adrenocortical adenomas, in
carcinomas (n = 17), and in normal adrenal glands (n = 8) by quantitative real-time RT-PCR. The amount of seladin-1/DHCR24
mRNA was significantly reduced in
carcinomas (total
RNA, 2.5 +/- 0.8 pg/ micro g) compared with the other groups (P < 0.01). Western blot analysis confirmed the
mRNA results. Similarly, in adrenal
malignancies, significantly reduced levels of expression of the
ACTH receptor gene were found. In the
adrenal cancer cell line H295R and in primary cultures from adrenocortical cells,
ACTH (1 nM) and
forskolin (10 micro M) effectively increased seladin-1/DHCR24 expression, confirming that seladin-1/DHCR24 is modulated by the
ACTH/cAMP-driven pathway. In summary, this is the first demonstration that seladin-1/DHCR24 expression is reduced in
adrenal cancer, suggesting that it might be viewed as a new potential marker of adrenal
malignancies.