25-Hydroxyvitamin D3 suppresses PTH synthesis and secretion by bovine parathyroid cells

Ritter, Cynthia S.; Armbrecht, H. J.; Slatopolsky, Eduardo; Brown, Alex

doi:10.1038/sj.ki.5000394

Cited by 191 publications

(120 citation statements)

References 32 publications

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“…Therefore in the absence of 1α-hydroxylase inhibitor clotrimazol, what we observed could be the mixed role of both 25(OH)D 3 and 1,25(OH) 2 D 3 Indeed, it was previously reported that 25(OH)D 3 binds to VDR with low affinity, but the binding affinity has been reported to be tissue specific [35,36]. In agreement with our observation, 25(OH)D 3 has recently been reported to suppresses PTH synthesis by parathyroid cells, possibly by direct activation of the VDR [37].…”

Section: Discussionsupporting

confidence: 91%

25-Hydroxyvitamin D3 is a natural chemopreventive agent against carcinogen induced precancerous lesions in mouse mammary gland organ culture

Xiang

Hawthorne

Vaishnav

et al. 2008

Breast Cancer Res Treat

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Despite the role of vitamin D 3 endocrine system in prevention of mammary gland transformation in animal models, use of 1,25(OH) 2 D 3 in clinical settings is precluded due to its toxicity in vivo. Therefore much effort has been placed in developing relatively non-toxic vitamin D analogs. Recently, with the discovery of the expression of 25-hydroxy vitamin D 3 1α-hydroxylase (CYP27B1) in multiple extrarenal organs, the functional role of prohormone, 25-hydroxyvitamin D 3 [25(OH) D 3 ], has been redefined. Since 25(OH)D 3 does not cause hypercalcemia and maintains relative high concentration in serum, it is possible that the prohormone can be converted to active hormone in mammary epithelial cells to provide chemopreventive effects. In the present study, we evaluated its functional significance using mouse mammary organ culture (MMOC) system. We first showed that 25(OH)D 3 1α-hydroxylase is extensively expressed in mammary ductal epithelial cells at both protein and mRNA levels, which is a prerequisite for 25(OH)D 3 to function in an autocrine/paracrine manner. However, we also observed that clotrimazol (1α-hydroxylase inhibitor) enhanced 25(OH) D 3 -induced CYP24 expression in breast cancer cells. In mammary glands derived from 1α-hydroxylase knockout mice, 25(OH)D 3 treatment in organ culture significantly induced CYP24 expression, indicating a potential direct effect of 25(OH)D 3 . In MMOC, 100-250 nM 25(OH)D 3 suppressed both ovarian hormone-dependent and -independent mammary precancerous lesions (induced by DMBA) by more than 50%, while the active hormone 1,25(OH) 2 D 3 (positive control) at 100 nM suppressed alveolar lesions by more than 80%. The inactive vitamin D 3 (negative control) at 100 nM suppressed alveolar lesions by only 20% (P > 0.05). We found that 25(OH)D 3 inhibits DMBA-induced mammary alveolar lesions (MAL) in a stage-specific manner: 25(OH)D 3 mainly inhibits the promotion stage of lesion formation. We conclude that 25(OH)D 3 could serve as a nontoxic natural chemopreventive agent for further development for breast cancer prevention.

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Section: Discussionsupporting

confidence: 91%

25-Hydroxyvitamin D3 is a natural chemopreventive agent against carcinogen induced precancerous lesions in mouse mammary gland organ culture

Xiang

Hawthorne

Vaishnav

et al. 2008

Breast Cancer Res Treat

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“…Moreover, vitamin D supplementation lowers serum PTH in the general population (21). Recent cell culture studies have demonstrated that 1␣-hydroxylase activity is present in bovine parathyroid cells, and these cells produce 1,25 dihydroxyvitamin D therein; this, in turn, acts locally to suppress PTH synthesis and secretion (22). This autocrine effect of vitamin D raises the possibility that circulating 25OHD may play a more important role than previously recognized in regulating serum PTH levels in CKD.…”

Section: Discussionmentioning

confidence: 85%

Hypovitaminosis D in Chronic Kidney Disease

Mehrotra¹,

Kermah²,

Budoff³

et al. 2008

Clinical Journal of the American Society of Nephrology

149

107

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“…Particularly in the elderly, serum 25-(OH)D levels are inversely correlated with PTH secretion (Kudlacek et al, 2003). One explanation for this phenomenon could be that in vitamin D insufficiency, CYP27B1-mediated production of 1,25-(OH) 2 D 3 in parathyroid gland cells is too low to effectively suppress PTH secretion (Ritter et al, 2006) and action on osteoclasts. Pilz et al (2008) found that low serum 25-(OH)D levels predict fatal cancer in general.…”

Section: Vitamin D and Calcium Actions And Interactions: Pathophysiolmentioning

confidence: 98%

Vitamin D and calcium insufficiency-related chronic diseases: molecular and cellular pathophysiology

Peterlik¹,

Cross²

2009

Eur J Clin Nutr

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A compromised vitamin D status, characterized by low 25-hydroxyvitamin D (25-(OH)D) serum levels, and a nutritional calcium deficit are widely encountered in European and North American countries, independent of age or gender. Both conditions are linked to the pathogenesis of many degenerative, malignant, inflammatory and metabolic diseases. Studies on tissue-specific expression and activity of vitamin D metabolizing enzymes, 25-(OH)D-1a-hydroxylase and 25-(OH)D-24-hydroxylase, and of the extracellular calcium-sensing receptor (CaR) have led to the understanding of how, in non-renal tissues and cellular systems, locally produced 1,25-dihydroxyvitamin D 3 (1,25-(OH) 2 D 3 ) and extracellular Ca 2 þ act jointly as key regulators of cellular proliferation, differentiation and function. Impairment of cooperative signalling from the 1,25-(OH) 2 D 3 -activated vitamin D receptor (VDR) and from the CaR in vitamin D and calcium insufficiency causes cellular dysfunction in many organs and biological systems, and, therefore, increases the risk of diseases, particularly of osteoporosis, colorectal and breast cancer, inflammatory bowel disease, insulin-dependent diabetes mellitus type I, metabolic syndrome, diabetes mellitus type II, hypertension and cardiovascular disease. Understanding the underlying molecular and cellular processes provides a rationale for advocating adequate intake of vitamin D and calcium in all populations, thereby preventing many chronic diseases worldwide.

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25-Hydroxyvitamin D3 suppresses PTH synthesis and secretion by bovine parathyroid cells

Cited by 191 publications

References 32 publications

25-Hydroxyvitamin D3 is a natural chemopreventive agent against carcinogen induced precancerous lesions in mouse mammary gland organ culture

25-Hydroxyvitamin D3 is a natural chemopreventive agent against carcinogen induced precancerous lesions in mouse mammary gland organ culture

Hypovitaminosis D in Chronic Kidney Disease

Vitamin D and calcium insufficiency-related chronic diseases: molecular and cellular pathophysiology

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