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Lookup NU author(s): Dr Judith Bulmer, David Kilby
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The active form of vitamin D (1,25-dihydroxyvitamin D-3, 1,25[OH](2)D-3) has well-established effects on bone metabolism and mineral homeostasis. However, recently it has become clear that 1,25(OH)(2)D-3 has potent antiproliferative and immunomodulatory actions that are not immediately linked to its role as a skeletal regulator. Both the nuclear receptor for 1,25(OH)(2)D-3 (vitamin D receptor, VDR) and the vitamin D-activating enzyme 1alpha-hydroxylase are expressed in a wide variety of nonclassic tissues, highlighting the potential for local autocrine-paracrine responses rather than traditional endocrine effects. Prominent among the tissues that express 1alpha-hydroxylase is the placenta-decidua, and this has raised important questions concerning the potential role of locally generated 1,25(OH)(2)D-3 as a modulator of fetal-placental development and function. When bound to the VDR, 1,25(OH)(2)D-3 regulates key target genes associated with implantation, such as HOXA10, whereas the potent immunosuppressive effects of 1,25(OH)(2)D-3 suggest a role in implantation tolerance. These observations are further supported by data from our group showing increased expression of 1alpha-hydroxylase and VDR in first-trimester trophoblast and decidua from human pregnancies. Studies by other groups have reported abnormal expression of 1alpha-hydroxylase in preeclamptic pregnancies, revealing a potential role for 1,25(OH)(2)D-3 as a regulator of placentation. The effect of vitamin D on reproduction has been further endorsed by murine gene knockout models for lot-hydroxylase and VDR, both of which are infertile. These observations and others are discussed in this article in which we postulate an active role for 1,25(OH)(2)D-3 in placenta-decidua. In particular, we describe how induction of the vitamin B-activating enzyme 1alpha-hydroxylase in early gestation might provide a mechanism by which environmental or dietary vitamin D can influence fetal-placental development. Copyright (C) 2004 by the Society for Gynecologic Investigation.
Author(s): Evans KN, Bulmer JN, Kilby MD, Hewison M
Publication type: Review
Publication status: Published
Journal: Journal of the Society for Gynecologic Investigation
Year: 2004
Volume: 11
Issue: 5
Pages: 263-271
ISSN (print): 1933-7191
ISSN (electronic): 1933-7205
URL: http://dx.doi.org/10.1016/j.jsgi.2004.02.002
DOI: 10.1016/j.jsgi.2004.02.002
