Endocrine Abstracts

JOINT2418

Objective: The expression of vitamin D receptor (VDR) and the role of 1,25-dihydroxyvitamin D3 (1,25(OH)D3) in human adrenal medulla is not well investigated. Previous reports showed that 1,25(OH)D3 accumulates in the nuclei of adrenal medullary cells in mice and increases expression of tyrosine hydroxylase gene in cultured bovine adrenal medullary cells. No genomic data regarding VDR mRNA expression in human pheochromocytoma or normal adrenal medulla has been reported. The aim of this study was to elucidate the expression of VDR in healthy human adrenal medulla and human pheochromocytoma cells, and to investigate the potential association between VDR presence and the clinicopathological characteristics of pheochromocytoma.

Design and Methods: A total of 31 pheochromocytoma cases with available tissue samples from surgical resection, 4 samples of healthy adrenal cortex and 4 samples of unaltered adrenal medulla as control group were analysed. The expression of VDR at the mRNA level was assessed by digital PCR in all pheochromocytoma cases and the control group. For pheochromocytoma patients, clinical manifestation, hormonal status and histopathological results were retrospectively assessed.

Results: VDR mRNA expression in adrenal medulla and pheochromocytoma cells was compared to the expression in the control adrenal cortex, set at 1.0. The median VDR mRNA expression in pheochromocytoma specimens was the lowest when compared to unaltered adrenal medulla and adrenal cortex (median expression = 0.05; range: minimum = 0.0, maximum = 0.56). Unaltered adrenal medulla specimens demonstrated higher VDR expression than pheochromocytomas, but lower than that observed in the normal adrenal cortex (median = 0.49; range: minimum = 0.32, maximum = 0.58). No statistically significant correlations were observed between VDR mRNA expression levels in pheochromocytomas and most clinical parameters evaluated in this study. However, VDR expression in tumour tissues was negatively associated with somatostatin receptor 2 (SSTR2) expression, taking into account the confounding factors of sex and the interaction with elevated 3-methoxytyramine concentration.

Conclusions: In our study, we present, for the first time, the expression of the vitamin D receptor (VDR) in human adrenal medulla and pheochromocytoma tissue. VDR expression at the mRNA level was detected in unaltered adrenal cortex, adrenal medulla, and pheochromocytoma cells, with quantification achieved through digital PCR. The highest median expression was observed in the adrenal cortex, followed by an intermediate median expression in the adrenal medulla, and the lowest one in pheochromocytoma cells. No correlation between VDR mRNA expression levels and the primary clinical features of the disease was identified.