A Novel Androgen–Vitamin D Link

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RESEARCH HIGHLIGHTS Nature Reviews Endocrinology | Published online 09 Feb 2018; doi:10.1038/nrendo.2018.14 BONE A novel androgen–vitamin D link Androgen deficiency in men, which observations were corroborated in mice, suggesting that androgen can result from normal ageing or human cell lines. stimulation decreases 24-hydroxy- prostate cancer therapy, is associated Next, the effect of PR loss on lase-dependent vitamin D3 with reduced levels of vitamin D3 and vitamin D-related gene expression inactivation. Indeed, DHT increased an increased risk of osteoporosis. Now, was investigated. In mouse proximal serum levels of vitamin D3 in these new research has uncovered a novel convoluted tubule (PCT) cells, mice, confirming the link between link between vitamin D3 metabolism Pgr-targeted small interfering RNA androgens and vitamin D homeostasis. and sex hormone levels, a finding that (siRNA) reduced levels of Cyp24a1 “Using modulators of PR, we want could be exploited therapeutically to (encoding 24-hydroxylase), a vitamin to further investigate the role of PR in treat vitamin D deficiency. D3-inactivating enzyme, whereas the metabolism of vitamin D,” explains Eui-Ju Hong and colleagues first human PGR overexpression increased Hong. “We also wish to investigate the assessed whether endogenous Cyp24a1 expression. Subsequent biosynthesis and metabolism of androgens altered androgen- ChIP-sequencing showed that vitamin D in renal tissue during responsive gene expression in the progesterone treatment increased PR pregnancy, during which the kidney, a known androgen target recruitment to the Cyp24a1 expression of sex steroid hormones organ. Dihydrotestosterone (DHT) promoter, inferring a transcriptional and their receptors is increased.” treatment markedly decreased renal mechanism for DHT-dependent Conor A. Bradley Esr1 (encoding oestrogen receptor , Cyp24a1 suppression. α ORIGINAL ARTICLE Lee, S. R. et al. ERα) and Pgr (encoding progesterone Consistently, DHT markedly 5α-dihydrotestosterone reduces renal Cyp24a1 receptor, PR) expression in reduced renal Cyp24a1 mRNA and expression via suppression of progesterone orchidectomized mice; these protein expression in orchidectomized receptor. J. Mol. Endocrinol. 60, 159–170 (2018) NATURE REVIEWS | ENDOCRINOLOGY www.nature.com/nrendo ©2018 Mac millan Publishers Li mited, part of Spri nger Nature. All ri ghts reserved. .

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