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25-hydroxyvitamin D3-1α-hydroxylase expression in normal and pathological parathyroid glands
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
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2002 In: Journal of Clinical Endocrinology & Metabolism, ISSN 0021-972X, Vol. 87, no 6, 2967-2972 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2002. Vol. 87, no 6, 2967-2972 p.
Identifiers
URN: urn:nbn:se:uu:diva-93559OAI: oai:DiVA.org:uu-93559DiVA: diva2:167079
Available from: 2005-10-17 Created: 2005-10-17Bibliographically approved
In thesis
1. Vitamin D Hydroxylating Enzymes and Analogues in Parathyroid Tumors and Breast Cancer
Open this publication in new window or tab >>Vitamin D Hydroxylating Enzymes and Analogues in Parathyroid Tumors and Breast Cancer
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In hyperparathyroidism (HPT) raised serum concentrations of ionized calcium is caused by increased secretion of parathyroid hormone (PTH) by parathyroid tumors. Active vitamin D, 1α,25-dihydroxyvitamin D3, is known to suppress PTH secretion and to reduce proliferation of parathyroid tumor cells.

The aim of this thesis was to examine expression of vitamin D hydroxylating enzymes, regulating the activation and inactivation of vitamin D and to study effects of vitamin D analogues, in parathyroid tumors and breast cancer.

The vitamin D activating enzyme, CYP27B1/25-hydroxyvitamin D3 1α-hydroxylase (1α-hydroxylase) and the vitamin D inactivating enzyme CYP24A1/25-hydroxyvitamin D3 24-hydroxylase (24-hydroxylase) were expressed in parathyroid tumors and breast cancer.

The parathyroid tumors had raised expression levels of 1α-hydroxylase and reduced levels of 24-hydroxylase in comparison to normal parathyroid glands, indicating ability for endogenous activation of vitamin D. The expression of 1α-hydroxylase may be of therapeutic advantage for local activation of non-1α-hydroxylated vitamin D analogues in tumor cells, thereby reducing unwanted hypercalcemic effects.

Three of five selected low calcemic vitamin D analogues had as efficient PTH suppressing effect, in bovine parathyroid cells, as three vitamin D analogues used clinically for treatment of secondary HPT.

The non-1α-hydroxylated vitamin D analogue EB1285 showed antiproliferative and PTH suppressive effects as well as transcriptional activity in parathyroid and breast tumor cells, respectively.

Ketoconazole, an inhibitor of vitamin D hydroxylating enzymes, suppressed PTH secretion and potentiated the effect of vitamin D analogues. Combined treatment with vitamin D analogues and specific 24-hydroxylase inhibitors may be important for future therapy.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2005. 59 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 78
Keyword
Surgery, hyperparathyroidism, breast cancer, vitamin D, CYP27B1, CYP24A1, vitamin D analogues, ketoconazole, vitamin D receptor, Kirurgi
National Category
Surgery
Research subject
Surgery
Identifiers
urn:nbn:se:uu:diva-6008 (URN)91-554-6361-4 (ISBN)
Public defence
2005-11-08, Rosénsalen, Kvinnokliniken, Akademiska sjukhuset ing 95, Uppsala, 09:15
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Available from: 2005-10-17 Created: 2005-10-17Bibliographically approved

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