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J Urol. 2007 Sep;178(3 Pt 1):1092-6. Epub 2007 Jul 20.

Testicular maturation arrest to testis cancer: spectrum of expression of the vitamin D receptor and vitamin D treatment in vitro.

Author information

1
Section of Urology and Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03755, USA. ajay.k.nangia@hitchcock.org

Abstract

PURPOSE:

We investigated the qualitative distribution of vitamin D receptor in human testis pathologies and performed an in vitro study of vitamin D receptor expression in a human testis cancer cell line model.

MATERIALS AND METHODS:

Qualitative immunohistochemical analysis of vitamin D receptor in testis tumors, normal testis and specimens from infertile patients was performed. The human embryonal carcinoma cell line NT2/D1 (American Type Culture Collection, Manassas, Virginia) was cultured. Vitamin D receptor expression was examined by Western immunoblot analysis after incubating the cells with 250 to 800 nM vitamin D, 10 to 70 nM testosterone, 2 nM calcium or a combination of the 3 products.

RESULTS:

Negative controls, synctiotrophoblasts and interstitial stroma did not stain positive for vitamin D receptor. Spermatogenic, Sertoli's, Leydig and tumor cells stained positive in all specimens. Embryonal carcinoma demonstrated more nuclear and cytoplasmic staining than other tumors. Vitamin D receptor expression was seen at 50 kDa in the cell line. Sequential concentrations of vitamin D increased vitamin D receptor expression intensity. Simultaneous addition of vitamin D and testosterone decreased the vitamin D receptor signal, as did testosterone alone. Delayed administration of vitamin D 5 hours after testosterone showed the return of vitamin D receptor expression. A combination of calcium, testosterone and vitamin D showed decreased or no vitamin D receptor expression. Calcium alone increased vitamin D receptor expression at later passages.

CONCLUSIONS:

To our knowledge this is the first description of vitamin D receptor in different primary testis pathologies and in an embryonal carcinoma cell line. The in vitro model showed that vitamin D receptor is an active receptor and it is inducible with the addition of vitamin D. Testosterone may be important for vitamin D receptor down-regulation. Calcium may be an important co-factor in vitamin D receptor expression.

PMID:
17644135
DOI:
10.1016/j.juro.2007.05.009
[Indexed for MEDLINE]

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