Expression of the novel adrenocorticotropin-responsive gene selective Alzheimer's disease indicator-1 in the normal adrenal cortex and in adrenocortical adenomas and carcinomas.
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.
Endocrine Unit, Department of Clinical Physiopathology, University of Florence, 50139 Florence, Italy.
Paola
P
Luciani
Pietro
P
Ferruzzi
Giorgio
G
Arnaldi
Clara
C
Crescioli
Susanna
S
Benvenuti
Gabriella
G
Nesi
Andrea
A
Valeri
Isabell
I
Greeve
Mario
M
Serio
Massimo
M
Mannelli
Alessandro
A
Peri
D000293:Adolescent; D000302:Adrenal Cortex / Q000502:physiology*; D000306:Adrenal Cortex Neoplasms / Q000503:physiopathology*; D018246:Adrenocortical Adenoma / Q000503:physiopathology*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D005576:Colforsin / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D018043:Receptors, Corticotropin / Q000235:genetics
D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D018043:Receptors, Corticotropin; D005576:Colforsin; D000324:Adrenocorticotropic Hormone; D044925:Oxidoreductases Acting on CH-CH Group Donors; C437069:3beta-hydroxysterol delta24-reductase; C499055:DHCR24 protein, human