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2018 ; 19
(6
): ä Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Role of Cryptochrome-1 and Cryptochrome-2 in Aldosterone-Producing Adenomas and
Adrenocortical Cells
#MMPMID29874863
Tetti M
; Castellano I
; Venziano F
; Magnino C
; Veglio F
; Mulatero P
; Monticone S
Int J Mol Sci
2018[Jun]; 19
(6
): ä PMID29874863
show ga
Mice lacking the core-clock components, cryptochrome-1 (CRY1) and cryptochrome-2
(CRY2) display a phenotype of hyperaldosteronism, due to the upregulation of type
VI 3?-hydroxyl-steroid dehydrogenase (Hsd3b6), the murine counterpart to the
human type I 3?-hydroxyl-steroid dehydrogenase (HSD3B1) gene. In the present
study, we evaluated the role of CRY1 and CRY2 genes, and their potential
interplay with HSD3B isoforms in adrenal pathophysiology in man. Forty-six
sporadic aldosterone-producing adenomas (APAs) and 20 paired adrenal samples were
included, with the human adrenocortical cells HAC15 used as the in vitro model.
In our cohort of sporadic APAs, CRY1 expression was 1.7-fold [0.75?2.26] higher
(p = 0.016), while CRY2 showed a 20% lower expression [0.80, 0.52?1.08] (p =
0.04) in APAs when compared with the corresponding adjacent adrenal cortex. Type
II 3?-hydroxyl-steroid dehydrogenase (HSD3B2) was 317-fold [200?573] more
expressed than HSD3B1, and is the main HSD3B isoform in APAs. Both dehydrogenases
were more expressed in APAs when compared with the adjacent cortex (5.7-fold and
3.5-fold, respectively, p < 0.001 and p = 0.001) and HSD3B1 was significantly
more expressed in APAs composed mainly of zona glomerulosa-like cells. Treatment
with angiotensin II (AngII) resulted in a significant upregulation of CRY1 (1.7 ±
0.25-fold, p < 0.001) at 6 h, and downregulation of CRY2 at 12 h (0.6 ± 0.1-fold,
p < 0.001), through activation of the AngII type 1 receptor. Independent
silencing of CRY1 and CRY2 genes in HAC15 cells resulted in a mild upregulation
of HSD3B2 without affecting HSD3B1 expression. In conclusion, our results support
the hypothesis that CRY1 and CRY2, being AngII-regulated genes, and showing a
differential expression in APAs when compared with the adjacent adrenal cortex,
might be involved in adrenal cell function, and in the regulation of aldosterone
production.
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